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KINSIM User`s Manual. Bruce A. Barshop Washington University

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1. 68 Output constant symbol overflow 69 Output calculation stack overflow 70 No output specified 71 Illegal output channel reference 72 Output constant overflow 73 Decode error in output constant 74 Too many output expressions EQUILIBRIUM GENERATOR 81 Nota binding equilibrium Too many complexes 83 Recursion in equilibria Too many components CHAPTER 4 PERFORMING A KINETIC SIMULATION The initial display in KINSIM is the main menu prompt KINSIM Version 3 3 Chemical Kinetic Simulation System Options V View mechanism M Load mechanism C Change concentrations K Change rate constants F Change output factors T Change time factors ON D Toggle display output OFF L Toggle list output OFF O Toggle binary output OFF P Toggle plot output OFF Toggle inclusion of real data OFF A Toggle agreement to real data S Save parameters R Restore parameters G Go simulate Q Quit Your option Single letter commands followed by a carriage return lt CR gt are used in response to this prompt Upper or lower case letters are acceptable 4 1 LOADING A MECHANISM In general the first option chosen will be M to load a mechanism A prompt will appear for the file name of the mechanism descriptor file which is the file created by the compiler Refer to appendix B for conventions of file specification When the mechanism descriptor file is successfully loaded the mess
2. C LINE 1 1 C ELSE IF MODE EQ INTMOD THEN IF LINE 1 1 EQ C LINE 1 1 ENDIF ELSE IF LOG THEN IF MODE EQ INTMOD THEN IF LINE 1 1 NE C LINE 1 1 C ELSE IF MODE EQ LOGMOD THEN IF LINE 1 1 EQ C LINE 1 1 ENDIF ENDIF ENDIF WRITE 2 1X A LINE 1 LENGTH END IF END DO END IMPLEMENTATION NOTES Page E 8 A similar scheme can be used to enable and disable VAX specific and RT 11 specific sections of files GETVALS FOR KINCOMP FOR QIOAST FOR and UTIL FOR using the delineators C VAX C VAX C RT1 C RT1 E 6 PROGRAM FLOW AND OVERLAYING The programs are modularized in accordance with their flow so as to facilitate overlaying The following diagrams should be useful in designing an overlay scheme These diagrams relate the root segments for each stage during the running of the compiler and simulator The entire list of subroutines needed in the branches can be determined from the lists of calls in the header notes l Il l RCTALZ EQCOMP GENEQB MAKMDB Il II II Il l KINCOMP l Il COMPILER Program Flow l l l l l l l l l l INIT LODMEC PRESIM DOSIM FINSIM IIl IIl IIl IIl Il l KINSIM l Il SIMULATOR Program Flow E 7 GRAPHICS ROUTINES NOT PROVIDED As mentioned above the routines in the GRAPHIC module make ref
3. will be separate pages of a single VERSAPLOT output APPENDIX D DATA FILE STRUCTURE The data files for input to KINSIM may either be real data files produced by the STOPFLOW data acquisition program or simulated data files produced by KINSIM itself The files are written in large fixed length records with each 512 byte record equivalent to one disk block The first record block of the file is a file header and contains general information about the experiment Subsequent blocks as needed contain the data themselves The data sections of real data files are simply consecutive values of optical transmission or absorbance recorded at fixed time intervals from the photomultiplier tube of the stopped flow apparatus The data sections of the simulated data files are more complex owing to the fact that at each time point there may be several output values The simulated data therefore is interdigitated at each time point each of the output values is written in turn DATA FILE STRUCTURE Page D 2 D 1 THE DATA FILE HEADER STRUCTURE The first block of the data file contains the following information FILECODE INTEGER 4 The file code identifies the file type so that an incorrect file can not be read by mistake CREATOR LOGICAL 1 10 The name 10 characters of the experimenter operating the stopped flow may be recorded Simulated data files bear the name SIMUL TIMEDATE LOGICAL 1 20 The time and date at the tim
4. 000D 01 ITERATIONS POINT 1 RUN TIME 4 500D 00 YMAX 1 200D 02 FLUX TOLERANCE 1 000D 01 RAPID EQUILIBRIUM YES RATE CONSTANTS K 1 1 000D 02 K 2 1 000D 02 K 2 0 000D 00 INITIAL CONCENTRATIONS E 1 000D 00 S 1 000D 02 ES 0 000D 00 P 0 000D 00 OUTPUT CONSTANTS X1 1 000D 00 X2 1 000D 00 TIME 1 2 0 000E 00 9 950E 01 0 000E 00 1 000E 01 9 453E 01 4 988E 00 2 000E 01 8 968E 01 9 847E 00 3 000E 01 8 497E 01 1 457E 01 4 000E 01 8 039E 01 1 917E 01 5 000E 01 7 594E 01 2 362E 01 6 000E 01 7 164E 01 2 794E 01 7 000E 01 6 748E 01 3 211E 01 8 000E 01 6 347E 01 3 614E 01 9 000E 01 5 960E 01 4 003E 01 1 000E 00 5 588E 01 4 376E 01 1 100E 00 5 231E 01 4 735E 01 1 200E 00 4 889E 01 5 078E 01 1 300E 00 4 562E 01 5 406E 01 1 400E 00 4 250E 01 5 720E 01 1 500E 00 3 954E 01 6 018E 01 1 600E 00 3 672E 01 6 301E 01 1 700E 00 3 405E 01 6 570E 01 1 800E 00 3 152E 01 6 824E 01 SAMPLE SIMULATIONS Page F 3 Oscillating systems The representations of the oscillating systems example textual mechanism descriptor files 3 and 4 at the end of the section on the compiler are particularly rigorous tests of functionality Before attempting these tests be forewarned that they will require a significant amount of CPU time to perform Feedback activation oscillator Try the feed back activation simulation with the values as specified below There should be about two cycles of oscillation in 1 8 seconds of simulation time MECHA
5. 01 2 682E 01 2 558E 01 2 390E 01 2 181E 01 APPENDIX G MAINTENANCE Chemical Kinetic Simulation System Washington University Medical School Department of Biological Chemistry THE INFORMATION ON THIS TAPE IS SUBJECT TO CHANGE WITHOUT NOTICE AND SHOULD THEREFORE NOT BE CONSTRUED AS A COMMITMENT BY THE AUTHOR HIS DEPARTMENT OR HIS SCHOOL THE AUTHOR ASSUMES NO RESPONSIBILTY FOR USE OR RELIABILTY OF THIS SOFTWARE UNDER ANY CIRCUMSTANCES Actually questions and suggestions are welcome If you have any problems or insights please contact us Prof Carl Frieden Department of Biological Chemistry Box 8231 Washington University School of Medicine St Louis Missouri 63110 Telephone 314 362 3344 Good luck and enjoy APPENDIX H HEADER NOTES In this place the header notes should be attached Page Index 1 INDEX Binary mechanism descriptor 3 1 Data file sise csuesrs D 1 converting D 3 READDF ces Nate D 3 D 5 WRITEDF ze D 3 D 5 data structure D 3 generating WRITEDF 3506232 22 50 D 3 header structure D 2 Implementation E 1 Installation E 1 compiler a an E 1 header notes E 6 H 1 overlaying E 8 simulator E 1 file i o nananana E 2 graphics ss a an E 1 to E 2 E 8 buffered i o E 1 storage t2 iwc ect awe E 3 KINCOMP description 3 1 error codes 3 9 opera
6. 171E 01 5 887E 01 6 584E 01 7 248E 01 7 850E 01 8 335E 01 8 610E 01 8 543E 01 8 043E 01 7 153E 01 6 000E 01 4 712E 01 3 395E 01 2 156E 01 1 147E 01 5 602E 00 3 911E 00 3 843E 00 4 136E 00 4 586E 00 5 215E 00 6 108E 00 7 420E 00 9 409E 00 1 247E 01 1 697E 01 2 286E 01 2 954E 01 3 653E 01 4 359E 01 5 063E 01 5 755E 01 6 422E 01 7 046E 01 3 0 000E 00 2 290E 03 6 782E 03 1 279E 02 2 106E 02 3 288E 02 5 046E 02 7 781E 02 1 226E 01 1 998E 01 3 411E 01 6 146E 01 1 173E 00 2 347E 00 4 733E 00 8 943E 00 1 501E 01 2 234E 01 3 020E 01 3 786E 01 4 445E 01 4 860E 01 4 848E 01 4 419E 01 3 837E 01 3 242E 01 2 662E 01 2 106E 01 1 582E 01 1 100E 01 6 795E 00 3 487E 00 1 416E 00 5 221E 01 2 375E 01 1 550E 01 1 401E 01 1 598E 01 2 121E 01 3 134E 01 5 045E 01 Page F 4 4 5 000E 01 0 000E 00 5 000E 01 4 957E 03 4 998E 01 2 076E 02 4 995E 01 4 823E 02 4 991E 01 9 155E 02 4 984E 01 1 584E 01 4 974E 01 2 627E 01 4 957E 01 4 301E 01 4 929E 01 7 088E 01 4 881E 01 1 193E 00 4 793E 01 2 068E 00 4 630E 01 3 698E 00 4 327E 01 6 726E 00 3 804E 01 1 196E 01 3 064E 01 1 936E 01 2 302E 01 2 698E 01 1 730E 01 3 270E 01 1 374E 01 3 627E 01 1 179E 01 3 821E 01 1 108E 01 3 892E 01 1 163E 01 3 837E 01 1 387E 01 3 613E 01 1 755E 01 3 245E 01 2 032E 01 2 968E 01 2 212E 01 2 788E 01 2 387E 01 2 613E 01 2 584E 01 2 416E 01 2 810E 01 2 190E 01 3 075E 01 1 925E 01 3 388E 01 1 612E 01 3 760E 01 1 240
7. 816E 01 5 972E 01 7 441E 01 9 318E 01 1 172E 00 1 481E 00 1 876E 00 2 380E 00 3 021E 00 3 828E 00 4 834E 00 6 072E 00 7 572E 00 9 353E 00 1 141E 01 1 374E 01 1 628E 01 1 895E 01 2 164E 01 Page F 6 4 5 000E 01 0 000E 00 5 000E 01 2 601E 04 5 000E 01 1 699E 03 4 999E 01 5 099E 03 4 999E 01 1 098E 02 4 998E 01 1 955E 02 4 997E 01 3 091E 02 4 995E 01 4 525E 02 4 994E 01 6 286E 02 4 992E 01 8 403E 02 4 989E 01 1 097E 01 4 986E 01 1 404E 01 4 982E 01 1 765E 01 4 978E 01 2 215E 01 4 973E 01 2 748E 01 4 966E 01 3 393E 01 4 958E 01 4 177E 01 4 949E 01 5 136E 01 4 937E 01 6 311E 01 4 922E 01 7 769E 01 4 904E 01 9 566E 01 4 882E 01 1 181E 00 4 854E 01 1 461E 00 4 819E 01 1 807E 00 4 776E 01 2 240E 00 4 722E 01 2 780E 00 4 655E 01 3 449E 00 4 573E 01 4 274E 00 4 472E 01 5 278E 00 4 352E 01 6 482E 00 4 210E 01 7 896E 00 4 048E 01 9 523E 00 3 866E 01 1 134E 01 3 667E 01 1 333E 01 3 459E 01 1 541E 01 3 247E 01 1 753E 01 3 038E 01 1 962E 01 2 841E 01 2 159E 01 2 661E 01 2 339E 01 2 506E 01 2 494E 01 2 379E 01 2 621E 01 1 230E 00 1 260E 00 1 290E 00 1 320E 00 1 350E 00 1 380E 00 1 410E 00 1 440E 00 6 053E 01 5 202E 01 4 380E 01 3 619E 01 2 947E 01 2 389E 01 1 958E 01 1 658E 01 2 420E 01 2 646E 01 2 820E 01 2 920E 01 2 928E 01 2 826E 01 2 615E 01 2 306E 01 2 285E 01 2 228E 01 2 211E 01 2 240E 01 2 318E 01 2 442E 01 2 610E 01 2 819E 01 2 715E 01 2 772E 01 2 789E 01 2 760E
8. A frame are complete and the main menu will reappear 4 2 3 Setting Time Parameters The Q amp A frame which prompts for time parameters is independent of the mechanism which is to be simulated However the relevant parameters to be set differ depending upon whether the mechanism involves reactions depicted as rapid equilibria If the mechanism does not contain equilibrium steps the following sort of display will appear when the option T is chosen the numbers shown are reasonable but arbitrary Delta time 1 0000E 03 lterations point 1 Run time 1 0000E 00 Ymax 1 0000E 02 Flux tolerance 1 0000E 01 Integral tolerance 1 0000E 04 The Delta time is the time step used in the solution of the mechanism the lterations point defines the number of time steps per output interval and the Run time is the total time course for the simulation The Ymax need only be set if a graphical output is to be used in which case it refers to the maximum value on the Y axis of the graph The flux tolerance and integral tolerance are parameters which control the numerical method used for the solution of the system These parameters determine how much computation will be required for the solution and so they should be set judiciously as described below As in any technique of numerical integration the solution of the chemical differential equations proceeds by dividing the time axis into intervals and using the de
9. O failure C CHARACTER filename The name of the output file C INTEGER numberpts skipcnt outcnt REAL runtime deltat File parameters ymax ymin baseline described above yvals MAXPTS MAXOUT are declared CHARACTER creator 10 comment 50 l timedate 20 INTEGER btype ctype REAL expnsn C C Code begins here C File parameters are set and the array yvals is filled C CALL WRITEDF MSGLVL LUN filename success yvals MAXPTS MAXOUT creator timedate comment runtime deltat skipcnt ymax ymin baseline numberpts outcnt btype ctype expnsn C IF success EQ 0 THEN Failure ELSE Another application might be a program to alter the values in an existing KINSIM format file As a simple example consider a program to multiply the values of a file by the factor 2 DATA FILE STRUCTURE Page D 5 PROGRAM MULTBY2 Example program skeleton C I Declarations as in preceding example C C Code begins here C CALL READDF MSGLVL LUN filename success yvals MAXPTS MAXOUT creator timedate comment runtime deltat skipcnt ymax ymin baseline numberpts outcnt btype ctype expnsn C DO 10 j 1 outcnt DO 10 i 1 numberpts 10 yvals i j yvals i j 2 C CALL WRITEDF MSGLVL LUN filename success yvals MAXPTS MAXOUT creator timedate comment runtime deltat skipcnt ymax ymin baseline numberpts outc
10. any character Typed by depressing the control key and then while keeping the control key depressed depressing the key X 2 WUMS BCCF Washington University Medical School Biological Chemistry Computing Facility PoE o a APPENDIX B CONVENTIONS FOR SPECIFICATION OF FILES Several options will require the user to specify the name of a file to be used for either output or input Loading a mechanism including real data and restoring simulation parameters require an input file Writing a listing outputting a simulated data file and saving simulation parameters require an output file The file name entered by the user may consist of up to 40 characters in the standard record management services file specification format DEV DIRINAME EXT VER where DEV is a mnemonic representing the physical device DIR the directory on that device NAME the file name EXT the file type extension and VER the version number of the file The device and directory may be omitted if the file may be assumed to reside in the user s Current default directory the version number defaults to the highest existing version number of the specified file With all file name prompts issued by KINSIM if there is an error in opening the file specified another prompt will be issued If the user Subsequently gives up or decides not to open the file typing nothing except a lt CR gt will return the program to the main menu Each type of file has a defau
11. both these equilibria are to be entered as dissociation constants 2 The output expressions include the names of species in the reaction scheme as well as output constants The first output expression will equal the concentration of the enzyme substrate complex EF times its extinction coefficient X1 plus the concentration of the substrate F times its extinction coefficient X2 minus some offset factor X3 At run time the values of the factors may be set for any particular display For example if the values of X1 X2 and X3 are set to 0 1 and O respectively the first output will simply equal the concentration of F The compiler will assemble a transcription of the mechanism representation which can be displayed at run time to refresh the user s memory The reaction steps will be numbered sequentially and the rate and equilibrium constants will be identified by these numbers The transcribed form of this particular mechanism will appear as follows FUM1 K1 K 2 K3 E F EF EF EM EM E M K 2 OUTPUT 1 EF X1 F X2 X3 OUTPUT 2 EM X4 M X5 X6 COMPILING A KINETIC MECHANISM Page 3 5 3 3 2 Bi Bi Enzyme Reactions The mechanisms below depict two schemes for bi bi enzyme reactions The first one is a compulsory order for substrate addition and the second one has a random addition The first OBIBI is represented with all rate governed steps and is simple to understand The second REBIBI has rapid equilibrium
12. equation may be calculated as a function of a changing concentration of species S in a single output expression S 1 S 4 n 1 L c S 1 c S 4 n 1 1 c S n L 1 c S n 6 The value last calculated for an output expression may be used in another output calculation In this case the output channel number to be referenced is indicated as an integer preceeded by an at sign For example the preceeding output expression could have been specfied in two output expressions 1 S 14 S 4 n 1 L c S 1 c S 4 n 1 2 1 1 c S 4n L 1 c S An COMPILING A KINETIC MECHANISM Page 3 4 3 3 EXAMPLE TEXTUAL MECHANISM FILES 3 3 1 Uni Uni Enzyme Reaction The mechanism depicted below represents the simple enzyme reaction catalyzed by fumarase In this mechanism E represents the enzyme F its substrate fumarate and M the product malate Fumarase mechanism Comment FUM1 Mechanism title E F EF EM E M Reactions OUTPUT Output expressions follow EF X1 F X2 X3 Two output EM X4 M X5 X6 expressions In the mechanism depicted above the characters to the right of the exclamation points are comments ignored by the compiler Notice the following features illustrated in the example 1 The first and third reactions are treated as rapid equilibria Although these two reactions are written from right to left as association and dissociation steps the constants associated with
13. is read arg1 arg99 These extra variables will be filled iff passed DESCRIPTION OF ARGUMENTS File IlO parameters MSGLVL Controls verbosity of messages INTEGER 4 MSGLVL 0 gt silent 1 gt terse 2 gt verbose LUN The logical unit number of the data file INTEGER 4 FILENAME The name of the data file CHARACTER SUCCESS Return status flag INTEGER 4 Data array parameters YVALS The array of data REAL 4 MAXPTS MAXOUT DANIDANDAIADAIAIDIADAINDINDINDIAINDIAINDIADAINDINDIDINDIAIAINAINDINADAININDINAIAININAINININIAINVNIAINAINNA 00000000 00000O MAXPTS The length dimension of YVALS INTEGER 4 MAXOUT The width dimension of YVALS INTEGER 4 Optional text arrays in file header CREATOR The name of the experimenter CHARACTER The length of this string does not matter but at most 10 bytes will be filled by READDF and at most 10 bytes will be written by WRITEDF TIMEDATE Time and date of the file creation CHARACTER As with CREATOR TIMEDATE is truncated if GT 20 byte COMMENT Associated comments for the file CHARACTER As with CREATOR COMMENT is truncated if GT 50 bytes DATA FILE STRUCTURE Page D 8 C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C C Required file parameters RUNTIME The duration of the experiment REAL 4 DELTAT The time step between output intervals REAL 4 SKIP
14. not on a DEC computer system see E 1 IV 3 If not using a VAX computer replace the ASTYES function QIOAST see E 1 VIl 4 Likely alterations will be needed in 1 FILOPN function see E 1 1 and subroutine WRTASC see E 4 in KINCOMP 2 UTIL module of KINSIM 3 GRAPHIC module of KINSIM see E 1 III and E 7 4 FILEIO module of KINSIM see E 1 VI 5 Also if changing to a version using LOGICAL 1 character storage perform the simple alterations outlined in E 4 6 If required design a linkage overlay descriptor see E 6 7 Build the system FORTRAN KINCOMP LINK KINCOMP FORTRAN SIMUL SOLVE QIOAST UTIL GRAPHIC LODMEC STRINGS FILEIO PROMPT Q amp A routines TRMSPCnnn LINK EXE KINSIM SIMUL SOLVE QIOAST UTIL GRAPHIC LODMEC STRINGS FILEIO PROMPT Q amp A routines TRMSPCnnn PLOT10 system VERSAPLOT system where Q amp A routines refer to either simply QATRAN or the two modules QASCRN and GETVALS see E 1 IV and TRMSPCnnn refers to either the TRMSPC640 module if using a PLOT10 compatible terminal TRMSPC125 if using a VT125 or the appropriate terminal dependent routines for your terminal The required components of the PLOT10 system and VERSAPLOT system are discussed in section E 7 APPENDIX F SAMPLE SIMULATIONS After the system is installed it is advisable to do extensive shake down Several examples plausible and im should be tried Note the few examples scattered throug
15. 2 000D 03 K 8 0 000D 00 INITIAL CONCENTRATIONS POOL 1 1 000D 02 A 0 000D 00 E 1 000D 00 EA 0 000D 00 B 0 000D 00 F 1 000D 00 FB 0 000D 00 SINK 1 0 000D 00 EB 0 000D 00 EBA 0 000D 00 OUTPUT CONSTANTS X1 5 000D 01 X2 X4 5 000D 01 5 000D 01 5 000D 01 SAMPLE SIMULATIONS TIME 0 000E 00 3 000E 02 6 000E 02 9 000E 02 1 200E 01 1 500E 01 1 800E 01 2 100E 01 2 400E 01 2 700E 01 3 000E 01 3 300E 01 3 600E 01 3 900E 01 4 200E 01 4 500E 01 4 800E 01 5 100E 01 5 400E 01 5 700E 01 6 000E 01 6 300E 01 6 600E 01 6 900E 01 7 200E 01 7 500E 01 7 800E 01 8 100E 01 8 400E 01 8 700E 01 9 000E 01 9 300E 01 9 600E 01 9 900E 01 1 020E 00 1 050E 00 1 080E 00 1 110E 00 1 140E 00 1 170E 00 1 200E 00 1 2 0 000E 00 4 494E 00 8 978E 00 1 345E 01 1 792E 01 2 239E 01 2 684E 01 3 129E 01 3 573E 01 4 016E 01 4 458E 01 4 898E 01 5 337E 01 5 773E 01 6 207E 01 6 637E 01 7 064E 01 7 487E 01 7 903E 01 8 313E 01 8 714E 01 9 104E 01 9 481E 01 9 841E 01 1 018E 02 1 049E 02 1 078E 02 1 102E 02 1 121E 02 1 135E 02 1 141E 02 1 140E 02 1 129E 02 1 109E 02 1 078E 02 1 036E 02 9 836E 01 9 216E 01 8 509E 01 7 732E 01 6 906E 01 3 0 000E 00 2 280E 04 1 195E 03 3 107E 03 5 988E 03 9 777E 03 1 444E 02 2 000E 02 2 652E 02 3 411E 02 4 303E 02 5 347E 02 6 555E 02 8 035E 02 9 769E 02 1 185E 01 1 436E 01 1 744E 01 2 120E 01 2 590E 01 3 170E 01 3 898E 01 4
16. 3 19 May 1983 lt CR gt lt LF gt NOT the lastest version but sufficient May 1990 The programs described constitute a flexible and powerful system for the simulation of full time course reactions In general there are three steps to simulating a given mechanism and each step is carried out by a separate program 1 Mechanism entry A chemical reaction scheme is typed using conventional chemical format The text editor of the user s choice is used to generate the textual mechanism descriptor file 2 Compilation The kinetic compiler is run which reads the textual mechanism file and assembles tables of information about the reaction scheme and the symbols used which are written in a binary mechanism descriptor file 3 Simulation The simulator is a general program which can in principle depict any chemical mechanism at all It reads the binary mechanism descriptor file output by the compiler to provide it with the necessary information to carry out the simulation of the given mechanism This manual describes the operation of the kinetic compiler and the simulator The programs described in this manual have been developed on a Digital Equipment Corporation VAX 11 780 computer at the Washington University Medical School Biological Chemistry Computer Facility WUMS BCCF Chapters 3 and 4 are the important user oriented sections Certain sections of this document are intended only to be of interest to local users at the WUMS
17. 7 1 Elective Abortion 4 8 4 7 2 Simulation Errors 4 8 4 8 RUN TIME ERRORS 4 9 4 8 1 Initialization Errors 4 9 4 8 2 Fatal Errors die ss 26 4 9 4 8 2 1 Mass Conservation Errors 4 9 4 8 2 2 Integration Errors 4 9 4 8 2 3 Floating Overflow And Divide by zero Errors 4 9 4 8 2 4 Excessive Computation 4 10 4 8 3 Catastrophic Errors 4 10 APPENDIX A ABBREVIATIONS AND SPECIAL SYMBOLS USED Page 2 APPENDIX B CONVENTIONS FOR SPECIFICATION OF FILES APPENDIX C AFTER THE SIMULATION SESSION APPENDIX D DATA FILE STRUCTURE D 1 THE DATA FILE HEADER STRUCTURE D 2 D 2 THE DATA STRUCTURE D 3 D 3 CONVERTING DATA D 3 APPENDIX E IMPLEMENTATION NOTES E 1 MODULE NOTES E 1 E 2 INCLUDEd files and PARAMETERS E 2 E 3 STORAGE REQUIREMENTS OF KINSIM E 3 E 3 1 Relationship Between KINCOMP And KINSIM E 5 E 4 REPRESENTATION OF CHARACTER DATA E 5 E 5 HEADER NOTES EXTRACTING AND SUPPRESSING SECTIONS OP CODES se ws wie whee deb aE E 6 E 6 PROGRAM FLOW AND OVERLAYING E 8 E 7 GRAPHICS ROUTINES NOT PROVIDED E 8 E 8 INSTALLATION SUMMARY E 10 APPENDIX F SAMPLE SIMULATIONS APPENDIX G MAINTENANCE APPENDIX H HEADER NOTES Index CHAPTER 1 OVERVIEW OF THE SIMULATION SYSTEM Version 3
18. 81 ET S2 OUTPUT S2 X1 S3 X2 S4 X3 S5 X4 S6 X5 S7 X6 S8 X7 S9 X8 Feedback inhibition Inhibited reaction Note that we take advantage of the leniency of the compiler here Since the compiler does not enforce mass balance the numeric suffixes of the species names are not treated as stoichiometries Refer to appendix F for sample parameter values COMPILING A KINETIC MECHANISM Page 3 8 3 4 SUMMARY TABLE OF MECHANISM SYMBOLS Kinetic reaction step Separates reactants and products Rapid equilibrium reaction step Separates components and complex Co reactants Separates species participating in a reaction step L x Chemical species Names are lt 10 characters begin with alphabetic nL x Reaction stoichiometry Indicates that species reacts with stoichiometry n L x An x Component stoichiometry Indicates component A is present with stoichiometry n L x Isomer Trailing apostrophe s may be used to distinguish species L x n Mass conservation Endows species with mass conservation attribute n Comment Text after exclamation point is ignored Mechanism title Text on line with dollar sign in column 1 used as title Section delimiter Asterisk in column 1 is used to separate the chemical and output equations Mathematical symbols 4 Used in the output equations Conventions used in this table x indicates any alphanumeric character L and A indi
19. BCCF The sections of local interest only are Chapter 2 Appendices B C and D Appendix E is a semi technical section with suggestions for the installation and implementation of the system CHAPTER 2 THE SIMUL COMMAND PROCEDURE At the WUMS BCCF the programs are integrated through the use of a single command procedure It is necessary to have two logical names in the process table Assign User Disk CFlab Simul Sim Assign User Disk CFlab Stopflow Sf To invoke the command procedure then type Sim Simul A parameter to the command procedure is used to determine which type of graphics terminal is being used That parameter can be passed directly Sim Simul VT125 or Sim Simul VT640 or the procedure will prompt the user when necessary If the terminal type is passed directly then further parameters can be used to be quickly executed as commands For example Simul Sim Simul VT125 Simul Compile Test Mec Simul Help Data Converting etc etc Extensive help is available on line through this command procedure The help facility makes use of the best features of the VAX VMS HELP utility and all users are urged to make use of it The option menu for the command procedure is Refer to appendix A for abbreviations used THE SIMUL COMMAND PROCEDURE Page 2 2 Commands are Edit edit a kinetic mechanism Compile compile an existing mechanism Simulate perform a simulat
20. CNT The number of time steps skipped between pts REAL 4 In general SKIPCNT is zero YMAX The maximum datum in the file REAL 4 Used to scale graphical displays YMIN The minimum datum in the file REAL 4 Used to scale graphical displays BASELINE The data baseline REAL 4 NUMBERPTS The number of data points INTEGER 4 OUTCNT The number of output channels number of points at each time point INTEGER 4 Archiving parameters ARG1 Archiving parameters may be included They are completely optional and may simply be left off of the argument list If passed however they must be ARG99 4 byte variables REAL 4 or INTEGER 4 or LOGICAL 4 The first three archiving parameters have been routinely in use for stopped flow files and they are explained below BTYPE For archiving only A code representing type of base line collected in stopped flow experiment INTEGER 4 BTYPE O no baseline 1 pretrigger 2 uninterrupted 3 interrupted CTYPE For archiving only A code representing type of optical conversion of data INTEGER 4 CTYPE 0 Transmission 1 Absorbance EXPNSN For archiving only Represents the response of the photomultiplier tube where a full scope face s voltage represents EXPNSN to 100 optical transmission The electronics which we use allow for recording with EXPNSN 0 50 80 90 or 95 APPENDIX E IMPLEMENTATION NOTES E 1 MODULE NOTES The program is modulari
21. E 01 4 184E 01 8 159E 00 4 575E 01 4 251E 00 4 808E 01 1 920E 00 4 899E 01 1 011E 00 4 927E 01 7 328E 01 4 928E 01 7 171E 01 4 913E 01 8 679E 01 4 880E 01 1 204E 00 4 817E 01 1 830E 00 4 703E 01 2 973E 00 1 230E 00 1 260E 00 1 290E 00 1 320E 00 1 350E 00 1 380E 00 1 410E 00 7 590E 01 7 987E 01 8 134E 01 7 911E 01 7 275E 01 6 306E 01 5 132E 01 8 766E 01 1 629E 00 3 164E 00 6 090E 00 1 083E 01 1 716E 01 2 442E 01 4 494E 01 4 122E 01 3 531E 01 2 788E 01 2 108E 01 1 631E 01 1 346E 01 5 062E 00 8 777E 00 1 469E 01 2 212E 01 2 892E 01 3 369E 01 3 654E 01 SAMPLE SIMULATIONS Page F 5 Feedback activation oscillator kinetic Compile the same mechanism without equilibrium steps as follows MECHANISM DESCRIPTOR OSCIL1P1 Oscillating system N 1 P 1 Kinetic K 1 K 2 K 3 K 4 POOL 1 A A E EA EA E B B F FB K 1 K 2 K 3 K 4 K 5 K 6 K 7 K 8 FB F SINK 1 E B EB A EB EBA EBA B EB K 5 K 6 K 7 K 8 OUTPUT 1 A X1 OUTPUT 2 B X2 OUTPUT 3 E EA X3 OUTPUT 4 EB EBA X4 SIMULATION PARAMETERS DELTA TIME 3 000D 02 ITERATIONS POINT 1 RUNTIME 4 500D 00 YMAX 1 200D 02 FLUX TOLERANCE 1 000D 01 INTEGRAL TOLERANCE 1 000D 03 RATE CONSTANTS K 1 3 000D 00 K 1 0 000D 00 K 2 1 000D 01 K 2 1 000D 01 K 3 5 000D 00 K 3 0 000D 00 K 4 1 000D 02 K 4 1 000D 03 K 5 1 000D 03 K 5 0 000D 00 K 6 1 000D 01 K 6 1 000D 03 K 7 1 000D 02 K 7 1 000D 03 K 8
22. FILE STRUCTURE Page D 3 D 2 THE DATA STRUCTURE The data points are equally spaced in time with the interval DELTAT At each time point the value of each data set up to MAXOUT sets is written in turn For example a data file consisting of three sets of data A B and C will be interdigitated thus ABCABC ABC 00011 1 mmm where A represents the value of the first data set at time n DELTAT n D 3 CONVERTING DATA Two subroutines have been written which should be of great help in creating suitable data files from sources other that the stopped flow apparatus and in altering data in existing KINSIM format files They are named READDF and WRITEDF and serve as simple interfaces between the casual programmer and the world of VAX FORTRAN I O These subroutines may be found in the object library SIMFIL OLB so that a data conversion program may be linked with them by the command LINK MYPROGRAM DRA1 BARSHOP SIMUL SIMFIL LIB A program to generate a data file might read a file in the appropriate format might read in data from a file or as entered by a user from the terminal In any case the program need only fill the array of data values and call WRITEDF For example DATA FILE STRUCTURE Page D 4 PROGRAM GENDF Skeleton program to C generate data file PARAMETER MAXPTS 1024 These are the maximum MAXOUT 8 dimensions of data array C INTEGER lun Logical unit number of output file success Flag where 1 successful
23. KINSIM User s Manual Bruce A Barshop Washington University Biological Chemistry Computing Facility 30 December 1983 CHAPTER 1 OVERVIEW OF THE SIMULATION SYSTEM CHAPTER 2 THE SIMUL COMMAND PROCEDURE CHAPTER 3 COMPILING A KINETIC MECHANISM 3 1 INTRODUCTION Smash 3 1 3 2 THE TEXTUAL MECHANISM DESCRIPTOR FILE 3 1 3 2 1 Chemical Equations 3 2 3 2 2 Output Equations 3 3 3 3 EXAMPLE TEXTUAL MECHANISM FILES 3 4 3 3 1 Uni Uni Enzyme Reaction 3 4 3 3 2 Bi Bi Enzyme Reactions 3 5 3 3 3 Feedback activation 3 6 3 3 4 Feedback inhibition 3 7 3 4 SUMMARY TABLE OF MECHANISM SYMBOLS 3 8 3 5 KINETIC COMPILER ERROR CODES 3 9 CHAPTER 4 PERFORMING A KINETIC SIMULATION 4 1 LOADING A MECHANISM 4 1 4 2 SETTING PARAMETERS 4 2 4 2 1 In house Version 4 2 4 2 2 Portable Version 4 3 4 2 3 Setting Time Parameters 4 3 4 3 SAVING AND RESTORING PARAMETERS 4 5 4 4 INCLUDING DATA 4 5 4 4 1 Real Data And Simulated Data 4 7 4 5 FITTING INCLUDED DATA 4 7 4 6 KINSIM OUTPUT OPTIONS 4 7 4 641 DISPIAV ss tw vee eae Patte we 4 7 AG 2 LISTE su rer onan Ses dE na 4 8 4 0 3 6 Ae ee 4 8 4 6 4 Output 4 8 4 7 INTERRUPTIONS OF SIMULATION 4 8 4
24. L V CHR 71 INT 13 LOG 80 CHR 14 SNG 53 U DBL where INT Storage required for one integer number SNG Storage required for one single precision real number DBL Storage required for one double precision real number LOG Storage required for one logical variable CHR Storage required for one character General values for the system dependent parameters are INT 4 SNG 4 DBL 8 LOG 4 CHR 4 The programs do not use the CHARACTER data type Rather symbolic names are filled into INTEGER arrays This is discussed further below Default values for the implementation adjustable parameters as written in the version of the program which we circulate are O M P M Q M R 8 S 150 T 20 U 20 V 10 With these values the expression for storage requirements expressed as a function of N and M becomes Storage bytes 245 M 16 M 2 36 N 24 N M 4056 Thus for a case with a maximum of 20 reactions and 20 species the COMMON storage requirements would be around 26 kilobytes IMPLEMENTATION NOTES Page E 5 There may be additional overhead however depending upon what course is adopted relating to the writing and reading of external data files The scheme for writing a data file which we have written subroutine WRTDF in module FILEIO involves a buffered I O scheme in which one block of data is held in COMMON FILBUF This involves an additional allocation for a block s worth PERREC of single precision values
25. LATION Page 4 10 certain sets of parameters may rarely give rise to a floating divide by zero error In the latter case itis possible that the integral tolerance should be lowered Alternatively with both these conditions the integration tolerance may need to be set to zero so as to activate the flux tolerance method If it is not possible to perform the simulation with rate constants which the user considers to be realistic it may be that the limitations of the computer simply do not permit the simulation in which case the mechanism must be simplified 4 8 2 4 Excessive Computation If the amount of computation exceeds installation defined limits see E 2 the simulation will halt with an error message indicating that the iteration limit exceeded At the WUMS BCCF there is no limit on computation for interactive use of the simulator since the user has the recourse to stop the simulation with a lt Control C gt at any time 4 8 3 Catastrophic Errors A catastrophic error could only arise fora completely unforeseen reason If KINSIM terminates with a system error message faithfully record the message and ask your system manager for advice APPENDIX A ABBREVIATIONS AND SPECIAL SYMBOLS USED Character codes lt CR gt or lt Return gt The carriage return key lt LF gt The line feed key lt ESC gt The escape key lt BS gt The backspace key lt Control X gt The control X character where X may be
26. ME CMN RDFCOM CMN SIMUL FOR SIMUL KINSIM GETOPT BADC SIMERR SHOWM OCALC PROMPT FOR PUTTFS PUTRDI TFLAB RDFLAB QATRAN FOR CSCRN1 FSCRN1 GET1TF GET1RP YESNO STRINGS FOR FILL LINLEN MOVC UPCASE SAME IFIND UTIL FOR FILOPN HANDL SOLVE FOR SOLVE DGEAR LUDATF GRAPHIC FOR PLTHD A method to do this automatically is outlined at the end of the next section E 5 HEADER NOTES EXTRACTING AND SUPPRESSING SECTIONS OF CODE The in line header comments in all the modules contain synoptic information which will be of use in understanding the system Since the header notes are delineated by comment lines beginning with C and C it is a simple matter to extract them using a program like the following PROGRAM EXTCOM Extracts header notes C CHARACTER LINE 80 LOGICAL 1 COPY FALSE INTEGER 4 EOF 0 C WRITE Enter name of source file READ A80 LINE OPEN UNIT 1 NAME LINE TYPE OLD WRITE Enter name of output file READ A80 LINE OPEN UNIT 2 NAME LINE TYPE NEW C DO WHILE EOF EQ 0 READ 1 Q A IOSTAT EOF LENGTH LINE IF EOF EQ 0 THEN COPY COPY OR LINE 1 3 EQ C OR LINE 1 3 EQ c IF COPY WRITE 2 1X A LINE 1 LENGTH COPY COPY AND LINE 1 3 NE C AND LINE 1 3 NE c END IF END DO END OONDABRWNDY A copy of these notes shoul
27. NISM DESCRIPTOR OSCIL1P1 Oscillating system N 1 P 1 K 1 K2 K 3 K4 K 5 POOL 1 A A E EA EA E B B F FB FB F SINK 1 K 1 K 3 K 5 K6 K7 K 8 E B EB A EB EBA EBA B EB K 8 OUTPUT 1 A X1 OUTPUT 2 B X2 OUTPUT 3 E EA X3 OUTPUT 4 EB EBA X4 SIMULATION PARAMETERS DELTA TIME 1 000D 02 ITERATIONS POINT 3 RUN TIME 1 800D 00 YMAX 1 200D 02 FLUX TOLERANCE 1 000D 01 RAPID EQUILIBRIUM YES RATE CONSTANTS K 1 5 000D 00 K 1 0 000D 00 K 2 1 000D 02 K 3 5 000D 00 K 3 0 000D 00 K 4 1 000D 01 K 5 1 000D 03 K 5 0 000D 00 K 6 1 000D 02 K 7 1 000D 01 K 8 2 000D 03 K 8 0 000D 00 INITIAL CONCENTRATIONS POOL 1 1 000D 02 A 0 000D 00 E 1 000D 00 EA 0 000D 00 B 0 000D 00 F 1 000D 00 FB 0 000D 00 SINK 1 0 000D 00 EB 0 000D 00 EBA 0 000D 00 OUTPUT CONSTANTS X1 5 000D 01 X2 5 000D 01 X3 5 000D 01 X4 5 000D 01 SAMPLE SIMULATIONS TIME 0 000E 00 3 000E 02 6 000E 02 9 000E 02 1 200E 01 1 500E 01 1 800E 01 2 100E 01 2 400E 01 2 700E 01 3 000E 01 3 300E 01 3 600E 01 3 900E 01 4 200E 01 4 500E 01 4 800E 01 5 100E 01 5 400E 01 5 700E 01 6 000E 01 6 300E 01 6 600E 01 6 900E 01 7 200E 01 7 500E 01 7 800E 01 8 100E 01 8 400E 01 8 700E 01 9 000E 01 9 300E 01 9 600E 01 9 900E 01 1 020E 00 1 050E 00 1 080E 00 1 110E 00 1 140E 00 1 170E 00 1 200E 00 1 2 0 000E 00 7 432E 00 1 487E 01 2 229E 01 2 971E 01 3 709E 01 4 443E 01 5
28. R gt lt LF gt TO SET THIS TO YES If flux tolerance is not enabled the delta time will be used directly as the integration time step In the case of a rapid equilibrium solution only the constraints of mass conservation will assure that the integration has not gone wildly out of bounds When routinely simulating a mechanism with equilibria it is a good idea to periodically repeat the simulation with the flux tolerance check enabled 4 3 SAVING AND RESTORING PARAMETERS Provision is made for resuming a simulation session without the need to go through the entire process of specifying all parameters The set of parameters which is to be restored at a later time must first be saved in a file Choosing option S save parameters will store the present parameter set in a file whose name is specified in the manner described in appendix B At any later time these parameters can be retrieved by chosing option R and specifying the name of the saved file 4 4 INCLUDING DATA Choosing option I include data will bring a prompt for the name of a data file The specified data set will be displayed or plotted along with the simulated output so that the simulated data may be directly compared to real data Once the specified file is opened a prompt frame will appear which will contain information about the data file including 1 the creator of the file 2 the time and date of its creation 3 the maximum and minimum value
29. There may also be overhead for the inclusion reading of external data e g for display superimposition If the data is to be read into memory there must be sufficient allocation for MAXPTS MAXOUT single precision values see Appendix A discussion of data file structure This overhead can be avoided if the data is held in a file e g a direct access file However please note that in that case enabling the run time option which calculates a sum of squares residual might seriously slow the program execution due to file I O operations at each iteration If a single precision version of KINSIM is desired the DOUBLE PRECISION variables may be declared as REAL also changing a few references of intrinsic double precision functions e g DABS To calculate the storage requirements of a single precision version of KINSIM evaluate the equation above with DBL SNG E 3 1 Relationship Between KINCOMP And KINSIM The routine which directly interfaces KINCOMP and KINSIM is LODMEC The READ statements in LODMEC must correspond to the WRITE statements in KINCOMP If the storage parameters of KINCOMP or KINSIM are changed it is possible that the resultant mechanism descriptor files from KINCOMP will be too large to fit in the memory of KINSIM All records in the mechanism descriptor file are preceeded with their lengths LODMEC checks for adequacy of its storage space at each READ so that in case there is an inconsistency the message Mecha
30. a binary file the binary mechanism descriptor file is created which is used as a load module to provide the run time program KINSIM with the information required to simulate a specific mechanism The text file can easily be created with the use of any editor When the compiler is run it will prompt for the name of an input textual mechanism descriptor file The file name is specified as outlined in appendix B The file will be read and the mechanism will be kinetically parsed If no errors are detected a prompt will be issued for the output file name for the output binary mechanism descriptor file 3 2 THE TEXTUAL MECHANISM DESCRIPTOR FILE The textual mechanism descriptor file consists of two major sections the first section contains the chemical equations and the second contains the output equations The chemical equations define the reaction scheme and the output equations define the variables to be graphed during the simulation Notes Delineation The two sections of the text file must be separated with a line containing an asterisk in column number 1 Comments An exclamation point in the text file indicates that the remainder of that line is a comment to be ignored by the compiler Title A line which has a dollar sign in column number 1 is used to entitle the mechanism the text on that line is included to identify the output of all simulations performed with that mechanism Including a title is entirely op
31. age Mechanism loaded will be displayed and then the main menu will return PERFORMING A KINETIC SIMULATION Page 4 2 4 2 SETTING PARAMETERS Having loaded a mechanism the user may proceed to set the simulation parameters The four major categories of parameters include 1 initial concentrations C 2 rate equilibrium constants K 3 output factor values F and 4 time parameters T Typing the one letter command corresponding to any of these options in the main menu followed by a lt CR gt will result in a tabular display of the given set of parameters each entry with an accompanying label After setting the parameters of interest the program will return to the main menu At any time while setting concentrations factors rate constants or time parameters typing a lt Control C gt will write the mechanism at the terminal to remind the user of the meaning of the various variables A lt CR gt or another lt Control C gt will return the user to the previous position in the present Q amp A frame The parameters are set in a series of question and answer Q amp A frames all of which adhere to one of two sets of conventions Which convention is used depends upon which version of the PROMPT module is used in the present implementation The version which is used on the VAX system at the WUMS BCCF the in house version allows for highly inter active screen oriented data entry A second veri
32. cate any alphabetic character n indicates any numeric character indicates any number of occurances of enclosed sequence COMPILING A KINETIC MECHANISM Page 3 9 3 5 KINETIC COMPILER ERROR CODES The compiler contains a simple error facility If an error is encountered in parsing the mechanism one of the following error messages will appear and the offending line of text will be displayed where applicable Module Error REACTION ANALYZER 21 Species found where delimiter expected Delimiter found where species expected Semicolon but unfinished step 24 Unexpected delimiter Reaction control block overflow 26 Species descriptor block overflow SPECIES ANALYZER 41 Zero length species name adjacent delimiters 42 Species with no components misplaced leading delimiter 43 Multiply specified isomerization misplaced apostrophe 44 Multiply attributed species 45 Invalid attribute value unexpected character at end of name 46 Component encountered after attribute isomer specification 47 Illegal character in species name unindentified error EQUATION COMPILER 61 Too many output calculation instructions 62 Syntax error in species name used in output expression 63 Variable name with non alphabetic first symbol 64 Missing operator after closing parenthesis 65 Unbalanced parentheses without 66 Unrecognized math operator 67 Unbalanced parentheses without
33. ce is set to zero the integration will be performed using an alternate method flux tolerance which uses a chemical criterion to assure that the integration remains within bounds When the flux tolerance method is in use the flux tolerance parameter defines the maximum fraction by which any species concentration may change in asingle iteration In this case the integration time step is chosen so as to keep the fractional concentration changes within the specified range The flux tolerance value may also come into use when Gear s method is enabled but only in the case of a violation of mass conservation Gear s method may under certain circumstances for example when a concentration is dropping very steeply give rise to negative concentrations If such a mass conservation violation ensues the integration step is re tried using a reduced integral tolerance up to 10 times Thereafter the step is retried using the flux tolerance method Since mass conservation is impossible unless the permitted flux tolerance is greater than 100 percent the situation will in general remit and Gear s method will be automatically re enabled for subsequent iterations In summary the use of two numerical methods assures that the system will stay in bounds in terms of numerical error Gear s method and also in terms of concentrations flux tolerance method The exact settings of these control parameters requires a certain amount of experimentation with ea
34. ch given system Note Reasonable default values are 0 1 for flux tolerance and 0 001 for integral tolerance If the simulation mechanism contains equilibrium steps the numerical approach is different since the concentration changes resulting from equilibria are fundamentally time independent and thus the table of partial derivatives is incomplete For this reason Gear s method can not be used on a system involving equilibria The flux tolerance method can be applied to the remaining system of differential equations However it is likely to lead to an excessively stringent solution and require a disproportionate amount of computational time because the incomplete system of differential equations will appear to be stiff For this reason when the mechanism contains equilibria the user may interactively enable and PERFORMING A KINETIC SIMULATION Page 4 5 disable the flux tolerance control The Q amp A frame for the time constants will appear as follows the numbers shown are reasonable but arbitrary Delta time 1 0000E 03 lterations point 1 Run time 1 0000E 00 Ymax 1 2000E 01 Flux tolerance 1 0000E 01 Equilibrium rapid NO The significance of the parameters are explained above with the exception of the equilibrium rapid switch This switch which may be set as YES or NO determines whether the flux tolerance method is to be used at each time step In order to get rapid simulation BE SURE lt C
35. d be attached in appendix H Among the information included in the header notes is the list of calls and references made by each routine This information is required if a linkage overlay scheme is needed IMPLEMENTATION NOTES Page E 7 A similar program can be used to change the required sections of FORTRAN source code for implementing the LOGICAL 1 version of the program something like the following PROGRAM CVTLI Converts code to logical 1 or integer versions C CHARACTER LINE 80 INTEGER 4 IOS 0 LOGICAL INT FALSE LOG FALSE INTEGER INTMOD 0 LOGMOD 1 MODE 1 C WRITE 6 Enter name of source file READ 5 A80 LINE OPEN UNIT 1 NAME LINE TYPE OLD WRITE 6 Enter name of output file READ 5 A80 LINE OPEN UNIT 2 NAME LINE TYPE NEW C WRITE 6 Convert to LOGICAL 1 L or INTEGER I READ 5 A LINE IF LINE 1 1 EQ l OR LINE 1 1 EQ i MODE INTMOD IF LINE 1 1 EQ L OR LINE 1 1 EQ l MODE LOGMOD C DO WHILE IOS EQ 0 READ 1 Q A IOSTAT IOS LENGTH LINE IF IOS EQ 0 THEN IF LINE 1 6 EQ C INT THEN INT TRUE LOG FALSE ELSE IF LINE 1 6 EQ C INT THEN INT FALSE ELSE IF LINE 1 6 EQ C LOG THEN LOG TRUE INT FALSE ELSE IF LINE 1 6 EQ C LOG THEN LOG FALSE ELSE IF INT THEN IF MODE EQ LOGMOD THEN IF LINE 1 1 NE
36. e of creation of the file COMMENT LOGICAL 1 50 Up to 50 characters of comment may be recorded RUNTIME REAL 4 The total time course of the run DELTAT REAL 4 The time interval between data SKIPCNT INTEGER 4 The number of time intervals between data points For real data files SKIPCNT is always equal to zero For simulated data files SKIPCNT could be non zero but we have never implemented such an option YMAX REAL 4 The maximum data value YMIN REAL 4 The minimum data value BASELINE REAL 4 The data baseline For simulated data files BASELINE is always equal to zero While the baseline has meaning mostly for real data files adjusting the baseline to be used in the display of simulated data files can shift the curves along the Y axis NUMBERPTS INTEGER 4 The number of data points NUMBERPTS DELTAT should always equal RUNTIME OUTCNT INTEGER 4 The number of output values at each time point For real data files produced by the STOPFLOW program OUTCNT always equals 1 BTYPE INTEGER 4 The type of data collection used in setting the baseline see STOPFLOW user s guide This value is preserved only for archiving purposes and is never used in the simulation CTYPE INTEGER 4 The coversion type absorbance transmission As with BTYPE an optional value EXPNSN REAL 4 The expansion of the voltage scale from the stopped flow apparatus expressed as EXPNSN to 100 percent transmission As with BTYPE an optional value DATA
37. erences to VERSAPLOT and PLOT10 subroutines 1 VERSAPLOT subroutines All the referenced routines conform to conventional pen plotter descriptions Subroutine PLOTS ibuf nloc ldev Used to initialize the plotter system The arguments are meaningless in newer versions of VERSAPLOT Subroutine PLOT x y ipen Processes straight line pen moves with the pen either up or down during movements IMPLEMENTATION NOTES Page E 9 X and y are coordinates defining the terminal position of the pen move ipen is a signed integer controlling the pen up down status reorigin and end of plot requests In this context all that is needed is ipen 3 Move to x y ipen 2 Draw to x y ipen 999 End of plot ipen 999 End of plot terminate all plotting Subroutine WHERE xnow ynow dfact Returns the present pen position and the drawing ratio factor Subroutine SYMBOL x y height itext angle nc Plots alphanumeric annotations at various angles and sizes Subroutine NUMBER x y height realnumber angle ndec Converts a floating point number to decimal equivalent and draws it on plot Refer to subroutine NUMBRE in GRAPHIC module 2 PLOT10 subroutines The terminal graphics routines are called in accordance with the PLOT10 conventions All routines to emulate the required subset of PLOT10 are provided for the VT125 in module TRMSPC125 If you are implementing terminal graphics on a system
38. formation regarding the data file The name of the data file will serve to remind the user of which experiment is under consideration Also the time maximum DTMAX and range of values Y range for the data set will be displayed so that the corresponding values for the simulation Run time and Ymax may be chosen to agree In fact note that upon including a data set these simulation values are automatically set equal to the corresponding values of the data set An example of the time parameters Q amp A frame for a kinetic mechanism after the inclusion of a data file is shown below Delta time 1 0000E 03 lterations point 1 Run time 4 5000E 00 Data Tmax 4 5000E 00 Ymax 1 1011E 01 Data Y range 1 1011E 01 Flux tolerance 1 0000E 01 Integral Tolerance 1 0000E 04 File name AD81N1301 DAT PERFORMING A KINETIC SIMULATION Page 4 7 4 4 1 Real Data And Simulated Data In general the data file will contain the output of a stopped flow run which was generated by the STOPFLOW data acquisition program The format of a data file is shown in appendix D In addition to real stopped flow data it is possible to include simulated data that is to superimpose one simulation on the output of a previous simulation This can be useful in comparing simulations made with different sets of parameters or with entirely different mechanisms The procedure is the same as for inclusion of real data but the file referenced is a file pre
39. hannel are set by the parameters MAXPTSFIL and MAXOUTFIL in the subroutines READDF and WRITEDF In the present implementation MAXPTSFIL 1024 and MAXOUTFIL 8 For successful completion MAXPTS must be LE MAXPTSFIL and MAXOUT must be LE MAXOUTFIL LINKAGE INSTRUCTIONS The function NEXTPT is part of the SIMFIL object library The MACRO function ARGLOC is taken from M T Scott s IO function library and is now also part of the SIMFIL object library USAGE CALL WRITEDF MSGLVL LUN filename success 000000000000 yvals MAXPTS MAXOUT creator timedate comment runtime deltat skipcnt ymax ymin baseline numberpts outcnt arg1 arg99 Input MSGLVL LUN filename creator comment runtime deltat numberpts outcnt btype ctype expnsn yvals MAXPTS MAXOUT DATA FILE STRUCTURE Page D 7 Optional input timedate If timedate is not passed present time and date will be written If passed must be by reference arg1 arg99 Archiving parameters may be written if passed Output success CALL READDF MSGLVL LUN filename success yvals MAXPTS MAXOUT creator timedate comment runtime deltat skipcnt ymax ymin baseline numberpts outcnt arg arg99 Input MSGLVL LUN filename MAXPTS MAXOUT Output creator comment runtime deltat numberpts outcnt btype ctype expnsn success Optional output yvals If yvals is not passed only the file header
40. hout this document The first sort of mechanisms to try are the simplest to assure that the compilation and numerical processes are operating correctly For example a mechanism like the following tests for correct solution of both a first and second order reaction First and second order reactions MECHANISM DESCRIPTOR First order and second order reactions K 1 K 2 A B 2C D K 1 K 2 OUTPUT 1 A0 A OUTPUT 2 1 C 1 CO SIMULATION PARAMETERS DELTA TIME 1 000D 02 ITERATIONS POINT 1 RUNTIME 1 000D 00 YMAX 1 000D 00 FLUX TOLERANCE 1 000D 01 INTEGRAL TOLERANCE 1 000D 05 RATE CONSTANTS K 1 1 000D 00 K 1 0 000D 00 K 2 1 000D 00 K 2 0 000D 00 INITIAL CONCENTRATIONS A 1 000D 00 B 0 000D 00 C 1 000D 00 D 0 000D 00 OUTPUT CONSTANTS AO 1 000D 00 Co 1 000D 00 The output constants AO and CO being set equal to the initial concentrations of A and C both outputs must be linear with time with slopes of one and two respectively You should confirm for yourself that this is true within truncation error Integral tolerance SAMPLE SIMULATIONS Page F 2 Simple enzyme mechanism A simple Michaelis Menten enzyme reaction such as the following uses both kinetic and equilibrium steps With the List option the output should match the following MECHANISM DESCRIPTOR Michaelis Menten reaction K1 K 2 E S ES ES E P K 2 OUTPUT 1 S X1 OUTPUT 2 P X2 SIMULATION PARAMETERS DELTA TIME 1
41. ion Display display stopped flow simul files Merge merge stopped flow simul files Debug debug a compiled mechanism DCL execute a one line DCL command Spawn enter a subprocess Reattach exit the subprocess Exit leave the room For additional help type HELP topic The options EDIT COMPILE and SIMULATE correspond to the three essential steps of the simulation process A simplified outline for executing the SIMUL command procedure is included below 1 If the mechanism to be simulated has already been successfully compiled proceed to step 3 If anew mechanism is to be generated or an existing mechanism is to be changed choose Edit The EDT editor will be invoked Refer to Chapter 3 for format of mechanism descriptor file 2 Choose Compile to compile the specified mechanism If an error ensues you may return to step 1 3 To carry out a simulation choose Simulate Refer to Chapter 4 for details of simulation A Load a mechanism by typing M lt CR gt B Set initial concentrations of reactants by typing C lt CR gt Return to option menu by typing lt ESC gt C Set values of the factors to be used in output of simulation by typing F lt CR gt Return to option menu by typing lt ESC gt D Set rate and or dissociation constants by typing K lt CR gt Concentrations and kinetic constants must be in the same units Return
42. ions may require that the KINSIM code be overlaid The irreducible storage requirements will be determined by the number of variables held in the KINSIM COMMON blocks The implementation adjustable variables are M MAXSPC max number of species N MAXRXN max number of reactions O MAXCPX max number of equilibrium complexes P MAXCPT max number of equilibrium components Q MAXAT1 max number of species to be held at fixed concs species with mass conservation attribute 1 R MAXOUT max number of output expressions S MAXISX max number of reverse Polish output calculation instructions T MAXFAC max number of adjustable output factors for output expressions U MAXVAL max number of fixed constant numerical values for output expressions V MAXNML max number of characters in a symbolic name IMPLEMENTATION NOTES Page E 4 These variables correspond to the parameters in the file SIMPAR CMN They may be changed simply by altering the contents of that single file and then rebuilding the KINSIM program The complete expression for the COMMON storage requirements is Storage bytes aM bM 2 cN dNM eO fO 2 gOP hQ IR jS KT l The coefficients are expressed in terms of the system dependent parameters for data storage a 2 INT 22 DBL V CHR b 1 DBL c 5 INT 2 DBL d 6 INT e 3 INT 1 DBL f 1 INT g 1 INT h 1 INT i 2 INT 1 DBL j 3 INT k 1 DB
43. le simulation 4 7 INTERRUPTIONS OF SIMULATION 4 7 1 Elective Abortion If the time required to complete a simulation is unacceptably slow or the user is simply impatient to reset parameters the simulation may be aborted at any point by typing a lt Control C gt 4 7 2 Simulation Errors A simulation may also be aborted due to errors In the event of such an error a descriptive message will be displayed at the bottom of the screen and the simulation will halt Typing a lt CR gt will bring up the main menu and corrective measures may be taken Refer to the section on run time errors for suggestions of corrective measures PERFORMING A KINETIC SIMULATION Page 4 9 4 8 RUN TIME ERRORS In the present context fatal errors refer to errors which will halt a simulation run Catastrophic errors refer to those which will halt the program execution Initialization errors refer to those which are detected before a simulation begins and which prohibit the run from being started 4 8 1 Initialization Errors These errors generally arise if a required parameter is not set A descriptive message will be given and in general the corrective measure is self evident For example if the delta time is zero the message Set delta time will appear and the run will be prevented until it is set to a non zero value An initialization error may arise if the binary output option is enabled and the number of points would exceed the maximum number of
44. lt file type If the file name is entered without an extension the appropriate file extension will be assumed The table below indicates the default file extensions for each type of file File type Default Textual mechanism descriptor MEC Binary mechanism descriptor SIM Saved simulation parameters SAV KINSIM format data file SDF Output listing file LST APPENDIX C AFTER THE SIMULATION SESSION 1 After terminating session any listings may be typed or printed using the file names that were specified at the time they were created TYPE listfilename PRINT listfilename 2 Any VERSAPLOT output generated option P may be plotted after terminating the session PLOT plotterlogicalname In the present implementation each plot consists of two files of the same name but different extensions The file name will correspond to the VMS logical name for the logical device PLOTTER The default file name is VPLT but it may be changed if prior to beginning the simulation session the logical name assignment is changed ASSIGN PLOTTER filename lt CR gt The two files of extension VPF and VVF corresond to the VERSAPLOT parameter file and vector file respectively Issuing the command PLOT filename lt CR gt will merge these files to create a raster which will be automatically queued for printing on the device queue SYS PLOT If multiple plots are made during the simulation session they
45. mitation that only the first eighty characters of each line of the text are read by the compiler If the steps are chemically consecutive they may be concatenated E SoS ES eS EP a b P If non consecutive steps are entered on one line they must be separated with a semicolon E 8S ES E El Presently only two types of mass conservation attributes are implemented for chemical species of the following types Attribute Action 0 Default Concentrations are checked to assure that they never become negative 1 The attributed species concentration is held constant at the initial level set by the user An attribute is assigned to a species by typing a left bracket followed by the attribute number immediatedly following a species name Any species may have only one attribute Each species need have its attribute specified only once even if the species appears in multiple steps For mass conservation attribute one constant concentration the number 1 may be omitted that is A is interpreted as A 1 COMPILING A KINETIC MECHANISM Page 3 3 3 2 2 Output Equations The output equations allow the concentration units used for a simulation to be converted to other units for example absorbance for direct comparison of simulated data to experimental data The output expressions are specified in standard FORTRAN style algebraic notation with the following rules and restrictions 1 Operand parame
46. moval of product Notice that the species represented as POOL is given a special mass conservation attribute of type 1 as itis represented as POOL 1 This if K 1 EQ 0 assures that the influx of Ais at a constant rate Similarly the SINK is limitless and if fixed at zero concentration even if K 5 is non zero the reaction will not reverse Although back reaction could simply be eliminated by making K 5 equal to zero with time there might be a danger of numeric overflow in the computer if the concentration of SINK is not kept at zero A noteworthy feature of this system is that it can sustain oscillations This is not only an extremely interesting phenomenon to study but also a very effective test for each installation of this simulator Refer to appendix F for sample parameter values COMPILING A KINETIC MECHANISM Page 3 7 3 3 4 Feedback inhibition The mechanism depicted below represents a scheme of feed back inhibition of an enzyme in a series of reactions OSCIL8P2 Oscillating system N 8 P 2 POOL 1 E8 S1 S2 S3 S4 S5 S6 S7 S8 S1 E1S1 E2S2 E3S3 E4S4 E5S5 E6S6 E7S7 E8S8 Constant infusion E1 S2 E2 S3 E3 S4 E4 S5 E5 S6 E6 S7 E7 S8 E8 S9 A series of baw bot Michaelis Menten reactions I ee E9 S9 E9S9 E9 SINK 1 Removal by final enzyme E1 2S9 E1 E1 S1 E1
47. nism Overflow is issued and the mechanism descriptor file is rejected E 4 REPRESENTATION OF CHARACTER DATA As mentioned above the characters of symbolic names are filled into INTEGER arrays rather than using CHARACTER or even LOGICAL 1 data types This is to assure maximal portability independent of the word size of the computer in question The storage can be decreased somewhat if the arrays to hold the symbolic names are declared as LOGICAL 1 or CHARACTER data type The greatest saving will actually be in the size of the KINCOMP output file rather than the dynamic memory Accordingly a routine in the compiler named WRTASC is provided which can write the text contained inan INTEGER array byte wise into the KINCOMP output file Changing the character storage element in the output file requires corresponding changes to be made in a few of the KINSIM modules At each place where a change is needed a declaration statement for an INTEGER variable should be replaced with the corresponding LOGICAL 1 statement At each of these places in the code the proper replacement line is provided as a comment and the places are all demarcated by comment lines beginning C LOG and IMPLEMENTATION NOTES Page E 6 C LOG If the FORTRAN compiler on your computer does allow LOGICAL 1 data type it is suggested that you implement these changes in the following modules KINCOMP FOR WRTASC COMMON INCLUDE FILES NAMES CMN FNA
48. nt btype ctype expnsn C IF success EQ 0 THEN Failure ELSE Success END IF END Header comments from the routines follow DATA FILE STRUCTURE Page D 6 000000000000 0000000000000000000000000000000O The subroutines READDF and WRITEDF provide a convenient means to read and write data files in the KINSIM format They return a status flag the INTEGER variable SUCCESS which is set to 1 for success or to O in the case of a failure Messages may also be output by these routines and the verbosity of the messages MSGLVL may be set to one of three levels Silent No messages Terse Error messages will be reported Verbose Error warning and success messages will be reported Error message will be written to the default output device file SYS OUTPUT READDF and WRITEDF require the calling program to allocate space for the storage of the file s data The array YVALS is the buffer for the data points which are equally spaced in time There may be more than one channel of data That is YVALS is a two dim ensional array and each channel is assumed to have the same number of points Thus the array YVALS is of dimension MAXPTS x MAXOUT and YVALS I J contains the l th point of the J th output channel Declared dimensions of YVALS must be passed to READDF and WRITEDF as the arguments MAXPTS and MAXOUT The maximum number of channels permitted in a file and max number of points per c
49. on of the PROMPT module the portable version has also been provided which is somewhat less sophisticated but which may be used on essentially any other computer 4 2 1 In house Version Each parameter corresponds to a field within the Q amp A frame and a prompt is issued for each field of the frame in turn The cursor will be positioned adjacent to the parameter which is next to be set If that parameter is not to be changed typing nothing except a lt CR gt will move the cursor to the next field or a lt BS gt will move the cursor to the previous field The value of a parameter may be changed simply by typing a new value A numerical value can be entered in exponential E type format as well as standard floating point F type format If while entering a value a lt Control U gt is typed all entry will be canceled and the previous value will be redisplayed Typing a lt Control W gt will repaint the screen When the contents of the particular Q amp A frame are satisfactory typing a lt LF gt or lt ESC gt will exit that frame Typing lt ESC gt will always bring about a return to the main menu Typing lt LF gt will return to the main menu if all of the parameters in the present set have been inspected If there are more parameters in the set of interest than fits in the present Q amp A frame typing lt LF gt will bring up the next Q amp A frame There are only 20 prompts in a single Q amp A frame so that if fo
50. points permissable in an output file In this case one should try to increase the delta time or if that is not permissable increase the iterations point 4 8 2 Fatal Errors 4 8 2 1 Mass Conservation Errors Probably the most likely simulation error will be violation of mass conservation The situation can be alleviated by either using a smaller integration time interval or a larger flux or integral tolerance If the time interval is decreased it may be desirable to increase the iterations point so as to maintain the same output interval 4 8 2 2 Integration Errors Rarely an error may arise if Gear s algorithm fails In such an instance increasing the integral tolerance may remedy the situation If this fails the integral tolerance may be set to zero so as to activate the flux tolerance method If there is still a failure it is possible that the mechanism is written incorrectly 4 8 2 3 Floating Overflow And Divide by zero Errors Occasionally a calculation may give rise to a value which is beyond the range able to be represented by the computer In particular the Gear algorithm may give rise to floating overflow errors when the partial derivatives are calculated if the concentration changes of certain species in the mechanism are strongly interdependent and the magnitude of certain rate constants is relatively large Decreasing the magnitude of the rate constants may remedy the situation Similarly PERFORMING A KINETIC SIMU
51. r example the simulation mechanism involves 25 species the first concentration prompt frame will concern only the first 20 species In this case to change the initial concentrations of the remaining 5 species the user must type lt LF gt to bring up the second Q amp A frame The next lt LF gt will bring about a return to the main menu PERFORMING A KINETIC SIMULATION Page 4 3 4 2 2 Portable Version There will be a prompt beneath the table of parameters asking to identify the parameter which is to be changed for example Change concentration In response to this prompt the user types the label of the parameter which is to be changed for example the name of the species whose concentration is to be set If the reply entered is not recognized as a label in the present Q amp A frame the Change prompt will be reissued If the reply is recognized as a label in the present parameter table a further prompt will be issued specifically asking for the value of the parameter by name A numerical value can be entered in exponential E type format as well as standard floating point F type format If there is an error in interpreting the number as typed the value will not be changed After the number and a lt CR gt is entered the entire table will be retyped to confirm the change When nothing except a lt CR gt is typed in response to the Change prompt it is assumed that the entries for the present Q amp
52. rivatives at each discrete time point to estimate the concentrations at the subsequent time point The user will specify a time interval for the output of simulated values the Delta time multiplied by the lterations point However if the integration interval is too large the numerical solution may verge out PERFORMING A KINETIC SIMULATION Page 4 4 of bounds To prevent this the program may carry out the integration of several smaller time steps until the user specified time interval has passed The division of the time interval is internal to the numerical solution routine and so is transparent to the user output will still occur at the intervals defined by the user The integral tolerance and flux tolerance parameters determine how the program performs the adjustment of the integration time step If the integral tolerance is non zero the integration will be performed using the so called backward differentiation formulae or Gear s method A matrix of partial derivatives which relates the inter dependence of the chemical concentration changes is used to determine the time step for the integration In this case the value of the integral tolerance parameter determines the fractional error in any concentration which will be tolerated by the numerical routine before an error is declared The time step is chosen so as to keep the estimated fractional truncation error less than the integral tolerance value If the integral toleran
53. s of the data 3 the baseline 4 the number of points in the data set and 5 the maximum time of the data set PERFORMING A KINETIC SIMULATION Page 4 6 File AD81N1301 DAT File creator BAB Creation date 14 05 43 13 NOV 81 Comments AMPDAse 50 ug ml AMP 100 uM pH 6 5 DYmax 1 1203E 01 DYmin 2 0473E 03 Baseline 1 9780E 03 Used 1 9780E 03 Y range 1 1011E 01 Used 1 1011E 01 Npts 1000 Used 1000 Run time 4 5000E 00 Used 4 5000E 00 Correct file Y N YES A prompt will be issued asking to verify that the file which was opened is the correct one If the reply is not Y es it is assumed that the wrong file has been opened and the main menu will reappear If the reply is Y es followed by a lt LF gt or lt ESC gt it is assumed that the correct file has been opened and that the values displayed are to be used without modification In this case the main menu will reappear and the included data set will appear on all subsequent plots or displays If the answer is Y es followed by a carriage return the data display parameters may be set as described above in section 2 1 In this case the display parameters which may be changed include 1 the baseline 2 the range of the graphical ordinate 3 the number of points displayed and 4 the run time which allows the data to be displayed on a different time scale After including a data set the Q amp A frame for the time constants will include three items of in
54. so as to conform with any DEC FORTRAN dialect the TTOUTBUF routines which it calls will require more work IMPLEMENTATION NOTES Page E 2 Note The TRMSPC125 module is easily modified to operate on the DEC VK100 GIGI terminal 2 Plotter dependent routines The GRAPHIC module has low level routines for hard copy plotting which are written to be compatible with the VERSAPLOT CALCOMP software package Although the software packages mentioned above are widely used if you have other graphic routines plotter calls in the GRAPHIC and module may have to be changed and a different TRMSPCnnn module may need to be written IV QATRAN FOR and QASCRN FOR correspond to the portable and the in house version of the question and answer module described in the user s manual and each has its own conventions for numeric entry They contain routines to be called from PROMPT Either one or the other is to be linked with KINSIM If QASCRN is used you must also be able to use or replace the GETVALS FOR routines V UTIL FOR has two essential routines which must be provided to open and close files FILOPN and FILCLS Also note that the routine GETMOD is optional if the program will be run only in interactive mode simply set MODE INTRCT VI FILEIO FOR is probably the most idiosyncratic module What you replace it with depends upon what sort of data file structure you elect to use VII The module QIOAST FOR is concerned with
55. st common output option The simulation will proceed with all output to the terminal in graphic form After the simulation stops the graph will remain displayed until the user types a lt CR gt A lt Control C gt will bring up a textual display of the mechanism superimposed upon the graphical output Another lt Control C gt ora lt CR gt will erase the textual display leaving the graphical output until a lt CR gt is typed PERFORMING A KINETIC SIMULATION Page 4 8 4 6 2 List Choosing this option a file is opened to receive the simulation output as a text stream so that it may later be typed or printed If in response to the Enter filename prompt the user enters TT the text stream will not be written to a file at all but will appear at the terminal Once the simulation is complete the main menu will reappear Note If the listing output is directed to the terminal the display option should be disabled Spurious results may arise otherwise 4 6 3 Plot The Plot option generates the files necessary for a VERSAPLOT hard copy graph of the simulation The Plot option is only active for a single simulation Refer to appendix C for instructions on printing the plots 4 6 4 Output This option is used to generate an unformatted output file which can be used to Include This is the manner in which simulated data files are created terminal output The Output option is active only for a sing
56. steps for addition of the substrates and dissociation of the products Note that there is only asingle rate governed step in the REBIBI mechanism Also note that the steps EB A EAB and EP Q EPQ could not be included as equilibrium steps in REBIBI to avoid the likelihood of violating the principle of microscopic reversibility OBIBI Ordered Bi Bi REBIBI Random equilibrium Bi Bi E A EA E A EA E B EB EA B EAB EQ P EA B EAB EPQ EQ E Q EQ P EPQ E Q EQ E P EP F1 P 7 F2 Q F1 P F3 E F2 Q F4 A F3 E F5 B F6 EA F7 EAB F8 EQ COMPILING A KINETIC MECHANISM Page 3 6 3 3 3 Feedback activation The mechanism depicted below represents a more complicated scheme of feed back activation of an enzyme It could be considered as a superficial representation of the phosphofructokinase reaction OSCIL1P1 Oscillating system N 1 P 1 Inexhaustible pool constant infusion POOL 1 Michaelis Menten reaction E A EA E B Non linear M M drain reaction Infinite sink F B FB F SINK 1 Produce activation E B EB EB A EBA EB S Output equations A X1 B X2 E EA X3 EB EBA X4 In this mechanism E represents the regulatory enzyme A its substrate and B its product The upper glycolyic pathway is represented as a reaction which results in a constant infusion of substrate The lower glycolytic pathway is represented as a non linear system i e a single enzyme F for the re
57. tement with the contents of the specified file If your FORTRAN compiler does not support the PARAMETER statement then you will have to replace the appropriate numerical value at each occurance of the parameter symbols throughout the code If your FORTRAN compiler does support the PARAMETER statement but does not allow parameters to be defined in terms of previously defined parameters you will have to alter the file COMPAR CMN so that the PARAMETER statements all have numerical values to the right of the equal signs Most parameters relate to the storage requirements of KINSIM One other parameter which is important to note when installing the system is the iteration limit MAXITR This parameter sets the maximum number of steps allowed within a single output interval Delta time times Iterations per point When that number of iterations is exceeded by either Gear s method or the flux tolerance method the simulation will be halted see section 4 8 2 4 This parameter is only important if your installation does not have a means of asynchronously aborting a run e g Control C see E 1 VIl In order to allow limitless computation MAXITR should be set to zero E 3 STORAGE REQUIREMENTS OF KINSIM The amount of memory required by KINSIM will vary depending upon the maximum mechanism complexity At the time of installation you should determine what limits you would like to establish for the maximum case On a smaller computer memory limitat
58. ters are indicated as the species names already used in the mechanism or may be names not previously used Species names refer to the species concentrations Names not present in the reaction scheme are used to define adjustable output factors to be set by the user at run time for example extinction coefficients 2 In addition to adjustable output factors which can be set at run time a mechanism may include fixed numerical values in its output calculations To include a value the number is entered preceeded by a number sign The number may be specified in integer floating point or exponential notation Thus the following are the same A 2 A 2 0 A 2 E0 3 The mathematical operators are 1 up arrow Exponentiation 2 asterisk Multiplication 3 slash Division 4 plus Addition 5 minus Subtraction 6 percent Logarithm Naperian 4 Mathematical operators have the standard priorities gt N gt gt 4 Parentheses can be used to resolve ambiguous expressions For example A B C adds A to the product of B and C and A B C multiplies C by the sum of A and log B 5 Output expressions may consist of more than one line of text provided that each unfininshed line ends with an underline character Thus it is possible to specify long calculations in a single expression For example the predicted saturation of a site obeying the Monod Wyman Changeux
59. the asynchronous interception of a control C typed by the user It is entirely VAX specific although it could easily be modified for use on any of the PDP 11 family of computers If you do not use it you have two choices 1 Remove all references to ASTSET and ASTYES from the other modules 2 Replace the routines with stubs RETURN END except for the logical function ASTYES which should just return value FALSE If you do this you will have less editing to perform on the bigger modules E 2 INCLUDEd files and PARAMETERS There are several INCLUDE statements throughout the code These statements direct the FORTRAN compiler to read the contents of a specified file as if that file were in line code The INCLUDE statements enable one to change COMMON allocation of the programs by changing a single file For example there is one file which is IMPLEMENTATION NOTES Page E 3 INCLUDE in every main module of KINCOMP COMPAR CMN which contains the parameters which determine the size of the programs COMMON arrays There are several INCLUDE d files for the simulator one which sets the corresponding dimension parameters SIMPAR CMN and also one file for each COMMON block The frequent INCLUDE statements may need to be changed to the appropriate syntax for other FORTRAN compilers If your version of FORTRAN does not have a statement analogous to INCLUDE you will have to edit the FORTRAN source files and replace each INCLUDE sta
60. tion 3 1 KINSIM Control C 4 2 4 7 to 4 8 E 2 CUO lt ee Stone res 4 8 including data 4 5 fitting os cota an Waste te 4 7 interruptions of simulation 4 8 E 3 loading mechanism 4 1 MONS brun ue d art 4 1 output options 4 7 85 0 EEE 4 7 Ses SN Ra 4 8 C 1 6 18 16 18 lt 6 ce See EE 4 8 Dl tises ess faut 4 8 C 1 saving and restoring parameters 4 5 setting parameters 4 2 integration constants 4 4 equilibrium 4 4 Q amp A frames 4 2 in house 4 2 E 2 portable sure 4 3 E 2 time constants 4 3 Mass conservation 3 2 Mechanism descriptor Page Index 2 chemical equations 3 2 example 3 4 to 3 7 F 3 F 5 TOTALE aus Paes omnes 3 1 3 8 output equations 3 3 SIMUL command procedure 2 1
61. tional COMPILING A KINETIC MECHANISM Page 3 2 3 2 1 Chemical Equations These equations are entered in standard chemical format Each species in the mechanism is represented by a unique name of up to ten characters which may be any combination of letters and numbers Monomeric species are represented by single letters and their complexes are represented as combinations of letters and numbers Numbers preceeding a species name signify multipliers and numbers following a component name signify stoichiometric constants For example A represents a monomeric species and AA or A2 represents the dimer of that species 2A2 represents two dimers of A and 2AB304 represents two molecules each of 1 A 3 B s and 4 O s Chemical steps in the mechanism are represented by equal signs Two equal signs in succession signify a step which is rate governed that is a step with both a forward and reverse rate constant A single equal sign specifies a rapid equilibrium step which will be forced to equilibrate at the beginning of each cycle in the integration of the mechanism Only one parameter is used to describe an equilibrium step and it is always a dissociation constant regardless of the direction in which the step is written There is a limit of forty chemical steps to a mechanism The steps may be entered individually on separate lines or as many as desired may be entered on a single line subject to the li
62. to option menu by typing lt ESC gt E Set timing and coordinate scaling parameters by typing T lt CR gt a Set the run time and ymax b As a first approximation use an integration point value of one and a delta time of 0 001 times the run time i If no equilibrium steps are included in the mechanism as a first approximation set Flux tolerance 0 1 and Integral tolerance 0 001 ii If equilibrium steps are in the mechanism as a first approximation set Flux tolerance 0 1 and Equilibrium rapid YES THE SIMUL COMMAND PROCEDURE Page 2 3 If real data is included the procedure is the same except that the run time and ymax are set automatically F Carry out the simulation by typing G lt CR gt G To terminate the simulation session type Q lt CR gt You will be returned to the level of the SIMUL command procedure 4 To exit the SIMUL command procedure choose Exit Note that there are many other functionalities in the SIMUL command procedure including data file display and manipulation Refer to the on line help CHAPTER 3 COMPILING A KINETIC MECHANISM 3 1 INTRODUCTION The kinetic compiler KINCOMP is the program which renders a human readable representation of a kinetic mechanism into an internal form Its input is a text file the textual mechanism descriptor file written according to the conventions outlined below The text file is parsed by the compiler and
63. viously generated by KINSIM itself through the O output option 4 5 FITTING INCLUDED DATA Choosing option A agreement to included data will enable the calculation of a sum of squares residual between one output channel of the included data and the values of one output of the simulation When this option is active the residual value will be displayed on the screen at the end of each successfully completed simulation The units of the residual are defined by the simulated output generally they are concentration 2 per unit time per point Note This function is of questionable usefulness when KINSIM is being run interactively The capability of calculating residual error is primarily intended to be used when KINSIM is being run in supervised mode under the control of another program The interactive user should rely upon visual inspection to refine the estimates of simulation parameters Enabling option A will in general hinder the performance of a simulation particularly where KINSIM is implemented on a smaller computer see implementation notes appendix E 4 6 KINSIM OUTPUT OPTIONS There are several options for the output of the simulation The output may be displayed at the terminal in a graphic form written as a formatted text stream written as an unformatted binary stream or rendered into a hard copy plot The main menu indicates which output options are enabled at any given time 4 6 1 Display This is the mo
64. which uses another terminal and you do not have a PLOT10 compatible package the following routines must be written Subroutine INITT640 ibaud Initializes terminal and terminal control system including establishment of output buffering as in TTOUTBUF module Clears screen sets terminal into graphics mode and homes graphics cursor Subroutine VWINDO xmin xrange ymin yrange Defines the physical coordinates of the terminal screen in terms of vitrual coordinates extending horizontally from xmin to xmin xrange and vertically from ymin to ymin yrange Subroutine MOVEA x y Moves graphics cursor to virtual coordinates x y Subroutine DRAWA x y Draws straight line from present virtual coordinates to virtual coordinates x y Subroutine POINTA x y Moves to virtual coordinates x y and draws one point there Subroutine HOME Moves graphics cursor to home position upper left Subroutine ANCHO ichar Enters alphanumeric mode if necessary outputs an alphanumeric character at present coordinates Input argument is a 7 bit ASCII non control character which is right justifiedwithin an integer word Subroutine TSEND Flushes all pending buffered graphics output IMPLEMENTATION NOTES Page E 10 E 8 INSTALLATION SUMMARY 1 First adjust the INCLUDEd files and PARAMETER statements as needed see E 2 and E 3 2 For the initial installation use the simpler transportable Q amp A package QATRAN especially if
65. zed so that hopefully no editing will be required on the big modules Note I expect the kinetic compiler KINCOMP FOR to run with very few modifications on almost any computer Probably the only thing to change is the routine to open files FILOPN Il SIMUL FOR SOLVE FOR and LODMEC FOR which are the heart of the run time program should not require significant changes either Thus you should be able to almost immediately run the program to generate listed output III GRAPHIC FOR also should be fully portable as it is written However the routines in GRAPHIC make calls to lower level routines for device dependent operations 1 Terminal specific routines The TRMSPCnnn FOR module contains the lower level graphics routines We presently maintain two versions TRMSPC640 is for use with the PLOT10 graphics package for use with the Digital Engineering VT640 terminal or any terminal compatible with the Tektronix 4010 series TRMSPC125 is for use with the ReGIS graphics package for use with the DEC VT125 terminal Our TRMSPC125 module is essentially an emulator of a limited part of the PLOT10 package To prevent the output of graphics to the terminal from becoming rate limiting during program the terminal I O operations should be buffered The PLOT10 package has this feature built in To emulate this feature of PLOT10 we have written the routines found in TTOUTBUF FOR While TRMSPC125 should be comparatively easy to modify

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