Protein-Ligand ANT System user manual for version 1.1 1
Contents
1. 1 5 2 Input Options e protein_file string protein filename e ligand_file string ligand filename e ligand_list string text file containing ligand filenames The keywords ligand_file and ligand_list may be used several times in a configuration file to specify for example a ligand database Also multi mol2 files may be used as input for docking and rescoring e use_gold_input string PLANTS reads in certain options from a GOLD input file only the following entries are considered protein_datafile ligand data file directory flip_planar_n flip_amide_bonds radius origin 1 5 3 Ligand Specific Data Ligand specific data is stored at the end of each ligand file inside the lt TRIPOS gt COMMENT block Protein Torsions Angles of rotatable bonds in the active site of the protein are stored in the following for mat This data is read for example in the rescoring mode and the protein s conformation is restored Format PLANTSPROTEINTORSIONS NUMBER_OF_INSTANCES PROTEIN_BOND_NUMBER ANGLE instance 1 PROTEIN_BOND_NUMBER ANGLE instance 2 etc 1 6 Output 1 6 1 Output Options e output_dir string name of output directory PLANTS automatically tries to create a subdirectory with the specified name and exits if the directory already exists to prevent overwriting existing data e write_protein_conformations value activate 1 or deactivate 0 output of protein conformations for scoring function2. standard clash2 e chemplp_clash_include_14 value activate 1 or deactivate 0 scoring of 1 4 interactions standard 0 25 e chemplp_ clash include HH value activate 1 or deactivate 0 scoring of hydrogen hydrogen interactions standard 0 Keywords affecting scoring function plp and plp95 e plp_steric_e value well depth for setric PLP interactions standard 0 4 e plp_burpolar_e value well depth for occluded polar PLP interactions standard 0 05 e plp_hbond_e value well depth for polar PLP interactions standard 2 0 e plp_metal_e value well depth for acceptor metal PLP interactions standard 4 0 e plp_repulsive_weight value weight for repulsive PLP interactions standard 0 5 e plp_tors_weight value weight for the ligand torsional potential standard 1 0 Keywords affecting scoring function chemplp e chemplp_weak_cho value activate 1 or deactivate 0 weak CH O scoring standard 1 e chemplp_charged_hb_weight value weighting factor multiplier for charged hydrogen bonds standard 2 0 e chemplp_charged_metal_weight value weighting factor multiplier for charged acceptor metal interactions standard 2 0 e chemplp_hbond_weight value weighting factor neutral neutral and neutral charged hydrogen bonds standard 3 0 e chemplp_hbond_cho_weight value weighting factor for CH O interactions stan dard 3 0 e chemplp_metal_weight value weighting factor for neutral accepto
3. MOL2 file and value the weight If a ligand forms a hydrogen bond with the specified protein atom the resulting score is multiplied by value2 only works with scoring function chemplp informa tion is written to features csv shape_constraint mol2 file weight shape constraint mol2 file specifies the molecule that is used for the volume overlap calculation the more ligand atoms overlap the better For an optimal atom overlap of a ligand and a shape atom value is added to the score value should be negative for example 3 0 surface_distance_constraint from to weight atomID defines a range bet ween from and to in A from the protein surface in which the specified ligand atoms defined by atomID you can specify multiple IDs separated by blanks should be placed If a ligand atom is placed inside the specified range weight is added to the score weight should be negative for example 3 0 ligand_intra_distance_constraint from to weight LatomID1 LatomI D2 de fines a distance range between from and to for two ligand atoms LatomID1 and LatomI D2 If the distance is inside the specified range weight is added to the score weight should be negative for example 3 0 protein_ligand_distance_constraint from to weight PatomID LatomID de fines a distance range between from and to for a protein PatomID and a ligand atom LatomID If the distance is inside the specified range weight is added to the score weight shoul
4. ach in stance of the ligand available in the protein e water_near_ligand_X YZ_N mol2 Water molecules in a maximum distance of 3A to any ligand atom e water mol2 All available water molecules 2 2 Bindingsite Definition by Ligand This mode calculates a sphere conatining the ligand molecule mol2 The user can specify an additional distance x that is added to the sphere radius PLANTS mode bind molecule mol2 x protein mol2 Output e bindingsite def Spherical bindingsite definition e PLANTSactiveSite mol2 Active site atoms as used inside PLANTS i e all atoms that lie inside the sphere only written if protein file specified e PLANTSactiveSiteResidues mol2 Complete active site residues only written if protein file specified 12
5. activate 0 output of merged protein files written to mergedStates mol2 standard 0 e write_merged_water value activate 1 or deactivate 0 output of merged water files written to mergedStates mol2 standard 0 e keep_original_mol2_description value keep 1 original mol2 description field as prefix for ligand naming standard 1 e merge_multi_conf_output value activate 1 or deactivate 0 merge of mul ticonformer output This is only carried out for ranked databases see above standard 0 e merge_multi_conf_character char character used for merging structure names standard _ e merge_multi_conf_after_characters value if merge character occured exactly value times from right to left the resulting prefix of the name is used for merging the structures keeping only the best scoring one for each ligand standard 1 1 6 2 Description of Output Files The following files are generated during a virtual screening or a rescoring run e ligand files the names are dependent on the input ligand filenames For each con formation generated by the cluster algorithm a suffix format _entry_XXXXX_conf_YY mol2 is added where XX XXX is the number of the molecule in a multi mol2 file and YY is the ligand conformation according to the cluster algorithm YY 01 is the best scoring pose e protein files ligandfilename_entry_X XXX X_conf_Y Y_protein mol2 e water molecule files ligandfilename_entry_X XXX X_conf_YY_wa
6. d be negative for example 3 0 Flexible side chains PLANTS allows protein side chains to be treated flexible PLANTS expects the protein file to include the backbone information according to the mol2 specification backbone atoms need to be marked with the BACKBONE tag If this information is not available PLANTS may behave in an unexpected way flexible_protein_side_chain_string string residue label of flexible side chain e g VAL123 flexible_protein_side_chain_number value residue number of flexible side chain e g 123 intra_protein_score_weight value weighting factor for the intramolecular pro tein score standard 0 3 fix_protein_bond value keep protein bond with bond number value fixed The use of flexible_protein_side_chain_number is recommended The file protein log can be used to check whether the side chains have been identified correctly In addition to the ligand conformations also the corresponding protein conformations can be written to files called protein_ligandfilename see section Output for details For rescoring purposes each ligand conformation file contains the torsion angles of the receptor side chains and rotatable donor groups Using such a conformation file as input will restore the bound receptor conformation 1 9 Multiconformer Docking PLANTS ic also capable of performing rigid body docking allowing for multiconformer docking of externally generated ligand conformations Depending on the sco
7. e flipping of bonds next to planar nitrogens standard 1 e force_flipped_bonds_planarity value activate 1 or deactivate 0 automatic planarity correction for flippable bonds standard 0 e force_planar_bond_rotation value activate 1 or deactivate 0 free rotation of planar bonds standard 1 e rescore_mode value perform simplex optimization during rescoring valwe simplex or only direct input conformation scoring value no_simplex standard simplex 1 2 Bindingsite e bindingsite_center valuel value value3 center coordinates of the binding site sphere no standard value e bindingsite_radius value radius of the binding site sphere no standard value 1 3 Cluster Algorithm e cluster_rmsd value RMSD similarity threshold for cluster algorithm standard 2 0 e cluster_structures value number of structures generated by the cluster algo rithm standard 10 1 4 Scoring functions Intermolecular protein ligand interaction scoring e scoring function string plp plp95 or chemplp standard chemplp e outside binding site penalty value scoring functions using precalculated grids use value to fill grid points outside the binding site definition standard 50 0 e enable_sulphur_acceptors value activate 1 or deactivate 0 scoring of sulphur acceptors standard 0 Intramolecular ligand scoring e ligand_intra_score string clash clash simple heavy atom clash terms or lj all atom Lennard Jones term
8. entries for features csv TOTAL_SCORE see above SCORE_RB_PEN see above SCORE_NORM_HEVATOMS see above SCORE_NORM_CRT_HEVATOMS see above SCORE_NORM_WEIGHT see above SCORE_NORM_CRT_WEIGHT see above SCORE_RB_PEN_NORM_CRT_HEVATOMS see above SCORE_NORM_CONTACT see above PLPPARTHBOND PLP hbond score PLPPARTSTERIC PLP steric contact score PLPPARTMETAL PLP metal interaction score PLPPARTREPULSIVE PLP donor donor and acceptor acceptor repulsion score PLPPARTBURPOLAR PLP buried polar atoms score polar atoms occluded by nonpolar ones LIG_NUM_CLASH number of ligand atoms with PLP score greater zero LIG_NUM_CONTACT number of ligand atoms with attractive PLP score LIG_NUM_NO_CONTACT number of ligand atoms with zero PLP score CHEMPARTMETAL CHEMSCORE metal interaction score CHEMPARTHBOND CHEMSCORE hbond score DON number of ligand donor atoms ACC number of ligand acceptor atoms UNUSED_DON number of unpaired ligand donors UNUSED_ACC number of unpaired ligand acceptors CHEMPLP_CLASH intra ligand clash score TRIPOS_TORS intra ligand torsion score INTRAPROT_CHEMPLP_PLP intra protein score only calculated for flex side chains ATOMS_OUTSIDE_BINDINGSITE number of ligand atoms outside binding site 1 7 Constraints Multiple instances of the following constraints can be specified 1 8 chemplp_protein_hb_constraint valuel value2 protein hbond constraint va lue1 defines the atom number according to the
9. i PLANTS Protein Ligand ANT System user manual for version 1 1 O Korb Oliver Korb uni konstanz de 1 Configuration File Settings PLANTS needs a configuration file that contains all data needed for docking virtual screening and rescoring The following sections describe the settings that can be adjus ted by the user For the case that no parameters are specified recommended standard settings are used PLANTS can then be executed in virtual screening mode by typing PLANTS mode screen yourconfigfile where yourconfigfile is the name of the configu ration file A rescoring of existing ligand poses can be carried out by typing PLANTS mode rescore yourconfigfile 1 1 Search Algorithm Since version 1 1 PLANTS offers predefined search speed settings which are set according to the scoring function chosen e search_speed value search speed setting value can be set to speed1 highest reliability slowest setting speed2 good reliability twice as fast as speed1 or speed4 modest reliability four times as fast as speed1 standard speed1 The parameters can be altered by adding one or more of the following keywords to the configuration file e aco_ants value number of ants standard 20 e aco_evap value evaporation factor p 0 1 e aco_sigma value iteration scaling factor o e flip_amide_bonds value activate 1 or deactivate flipping of amide bonds stan dard 0 e flip_planar_n value activate 1 or deactivat
10. r metal in teractions standard 6 0 e chemplp_plp_weight value weighting factor for PLP interactions standard 1 0 e chemplp_plp_steric_e value well depth for setric PLP interactions standard 0 4 e chemplp_plp_burpolar_e value well depth for occluded polar PLP interactions standard 0 1 e chemplp_plp_hbond_e value well depth for polar PLP interactions standard 1 0 e chemplp_plp_metal_e value well depth for acceptor metal PLP interactions standard 1 0 e chemplp_plp_repulsive_weight value weight for repulsive PLP interactions stan dard 1 0 e chemplp_tors_weight value weight for the ligand torsional potential standard 2 0 e chemplp_lipo_weight value weighting factor for lipophilic interactions stan dard 0 0 e chemplp intercept_weight value intercept value standard 20 0 1 5 Input 1 5 1 Atom Typing PLANTS exclusively uses the MOL2 file format thus MOL2 files including bond connec tivity must be provided for all input files PLANTS expects correct MOL2 atom and bond types This is needed for the correct identification of rotatable bonds and char ged functional groups and may influence docking and virtual screening performance Especially take care for the following cases e COO oxygens should get O co2 and not a combination of O 3 and O 2 please deprotonate COOH e guadinium carbocation should get C cat nitrogens N pl3 e positively charged sp3 nitrogen should get N 4
11. ring function e g chemplp only rotatable donor groups in the ligand will be treated flexible It is also possible to use rigid body docking in conjunction with flexible protein side chains not available in rigid_all mode e rigid ligand value activate 1 or deactivate 0 rigid ligand docking standard 0 e rigid_all value activate 1 or deactivate 0 rigid protein and rigid ligand docking standard 0 1 10 Water Explicit water molecules can be used during docking by adding one or several of the following keywords to the configuration file e water_molecule X Y Z r t s X Y and Z specify the center of the sphere inside which the water molecule is allowed to move and r the radius of the sphere This is the default mode For a detailed description see below It is also possible to fix the water molecule s translation by setting t 0 and adding a switching degree of freedom with s 1 In this case the water molecule can rotate and it is switched on or off by the search algorithm e water_molecule_definition filename MOL2 file that contains a single water molecule the position and orientation is arbitrary e water_protein_hb_weight value weight of water protein hydrogen bonds stan dard 1 0 e water_ligand_hb_weight value weight of water ligand hydrogen bonds stan dard 1 0 e water_water_hb_weight value weight of water water hydrogen bonds standard 1 0 10 e no_water_ligand_hb_penalty value penal
12. s chemplp standard 0 e write_protein_bindingsite value write protein binding site only activate 1 or deactivate 0 standard 0 e write_protein_splitted value write fixed and dynamic parts of the protein in separate files activate 1 or deactivate 0 standard 0 e write_rescored_structures value activate 1 or deactivate 0 output of resco red structures standard 0 e write multi mol2 value activate 1 or deactivate 0 output of multi mol 2 files standard 1 e write_ranking links value activate 1 or deactivate 0 output of ranked soft links requires write_multi_mol2 0 The links are stored in subdirectory ranking Unavailable when using explicit water molecules standard 0 e write_ranking multi_mol2 value activate 1 or deactivate 0 output of a sor ted multi mol2 file requires write_multi_mol2 1 Unavailable when using explicit water molecules Warning this option makes heavy use of the hard disk and the sorting process may take some time depending on the size of the virtual screening The output file is stored in subdirectory ranking standard 0 e write_per_atom_scores value activate 1 or deactivate 0 output of per mole cule atom scoring values partial atom charges are replaced standard 0 e write_merged_ligand value activate 1 or deactivate 0 output of merged li gand files written to mergedStates mol2 standard 0 e write_merged_protein value activate 1 or de
13. ter_ZZ mol2 whe re ZZ is the water molecule identifier e bestranking csv contains the score values the number of scoring function eva luation and the docking time for each best ranking ligand pose ranking csv same as bestranking csv but for all ligand poses features csv information about partial scoring function terms for all ligand poses constraints csv information about constraints for all ligand poses protein log information about the protein setup ligand log information about the ligand setup and the docking run score log scoring function parameters optimizer log information regarding the search algorithm settings Explanation of the header entries for ranking csv and bestranking csv TOTAL_SCORE scoring function value obtained during docking SCORE_RB_PEN TOTAL_SCORE plus penalty value for each ligand rotatable bond SCORE_NORM_HEVATOMS TOTAL_SCORE divided by number of ligand heavy atoms SCORE_NORM_CRT_HEVATOMS TOTAL_SCORE divided by cubic root of number of ligand heavy atoms SCORE_NORM_WEIGHT TOTAL_SCORE divided by molecular weight of ligand SCORE_NORM_CRT_WEIGHT divided by cubic root of molecular weight of ligand SCORE_RB_PEN _NORM_CRT_HEVATOMS SCORE_RB_PEN divided by cubic root of number of ligand heavy atoms SCORE_NORM_CONTACT TOTAL_SCORE divided by number of protein ligand contacts EVAL number of scoring function evaluations TIME docking time Explanation of the header
14. ty value that is added if no water ligand hydrogen bond is formed standard 0 0 e water_enable_penalty value penalty value that is added if a water molecule is active standard 8 0 If the water molecule is displaced by a ligand and moved outside the sphere the water molecule has no score contribution The weighting factors are only used for CHEMS CORE hydrogen bonding part of scoring function chemplp which is recommended for docking with explicit water molecules Scoring function plp may also be used but in this case only a water molecule s translational degrees are optimized and the above parame ters have no effect For each complex conformation also a water molecule conformation is written if it has not been displaced by a ligand 11 2 Special Modes Besides virtual screening and rescoring PLANTS also offers some special execution mo des 2 1 Molecule Splitting The molecule splitting mode allows to separate several molecules available in a single mol2 file This may be especially of interest when a complete PDB file is processed with SPORES and the protein the ligands and the water molecules are expected to be availa ble in separate files To start PLANTS in splitting mode type PLANTS mode split molecule mol2 The output then consists of the following files e protein mol2 The molecule that is expected to be the protein plus metal ions e ligand_X YZ_N mol2 Ligand with residue label XY Z N increases for e
Download Pdf Manuals
Related Search