DOCK 6.8 This is a release of DOCK with updated scoring functions including the new pharmacophore matching similarity score as described in reference [1] and a completely revamped Descriptor Score that allows for different combinations of various scoring functions to be used simultaneously (users should note that "descriptor score" in earlier versions of DOCK only allowed for footprint scoring). NEW IN DOCK 6.8 ###New Scoring Functions### Two new scoring functions were added: pharmacophore score [1], and descriptor score [see the manual]. Pharmacophore: Calculates the pharmacophore overlap between a candidate and a reference molecule. In addition, the python wrapper, mol2bild.py, can be employed to visualize the pharmacophores. Descriptor Score: Descriptor Score was completely overhauled. Presently, descriptor score is now a wrapper that allows multiple scoring functions to be employed simultaneously. Please refer to the manual for the complete list of scoring functions supported by descriptor score. Four similarity-based scoring functions were added as part of descriptor score: pharmacophore score, Tanimoto score, Hungarian matching similarity score, and volume overlap score. Hungarian matching similarity score, Tanimoto score and volume overlap score, new to DOCK, can only be called using descriptor score. ###Internal Energy Scoring Function### Optimization of the internal energy scoring function code and the addition of two parameters: a) The code has been optimized for calculating the repulsive VDW term. "internal_energy_rep_exp", when set to its default value of 12, results in a significant speedup in certain cases. Values other than 12 are computed as in previous versions of DOCK. b) The term "internal_energy_cutoff" has been added such that all conformers with an internal energy greater than the cutoff are pruned. c) The addition of the term "pruning_conformer_score_scaling_factor", a divisor of the pruning_conformer_score_cutoff, ensures that pruning becomes more stringent as flexibly-grown molecules proceed layer-by-layer. ###Miscellaneous### DOCK now supports builds using Intel compilers with either MPICH2 or Intel MPI parallelism. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ DEPRECATED FEATURES 1. For a variety of reasons still under active development, amber_score cannot effectively be used as a secondary_score. This function was temporarily deprecated in 6.1, and using input parameter amber_score_secondary causes program termination. The recommended protocol is to perform two sequential DOCK runs where the output ligand poses from the first run are rescored specifying amber_score as the primary_score in the second run. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ BUG FIXES Some bug reports have not yet been processed, but several important bugs have been fixed since the last release. For DOCK: Incorrect H-bond label assignment. This prevented assigning the first atom of a molecule as a hydrogen-bond acceptor or donor. Incorrect HA_RMSDm in some situations. In one case this could potentially produce an inaccurately small HA_RMSDm value. In another case if input parameter use_rmsd_reference_mol=no division by zero was possible leading to an HA_RMSDm value that was not an accurate maximum. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ INPUT PARAMETER CHANGES AND THEIR DEFAULT VALUES Changed: The order of input parameters has changed, the first question now is "conformer_search_type [flex] (rigid | flex):", which is equivalent to the parameter "flexible_ligand [yes] (yes no):" in earlier versions. The input parameters, "multigrid_score_use_euc [yes] (yes no):" and "multigrid_score_use_cor [no] (yes no):" have been combined into one question: "multigrid_score_foot_compare_type [Euclidean] (Pearson Euclidean):". "multigrid_score_use_norm_euc [no] (yes no):" was changed to "multigrid_score_normalize_foot [no] (yes no):" and is now only asked if multigrid_score_foot_compare_type is set to "Euclidean". A number of input parameters have been renamed. The bulk of these stem from Descriptor Score: Old Name New Name descriptor_score_primary footprint_similarity_score_primary descriptor_score_secondary footprint_similarity_score_secondary desc_use_footprint_reference_mol2 fps_score_use_footprint_reference_mol2 desc_footprint_reference_mol2_filename fps_score_footprint_reference_mol2_filename desc_use_footprint_reference_txt fps_score_use_footprint_reference_txt desc_footprint_reference_txt_filename fps_score_footprint_reference_txt_filename desc_foot_compare_type fps_score_foot_compare_type desc_normalize_foot fps_score_normalize_foot desc_foot_comp_all_residue fps_score_foot_comp_all_residue desc_choose_foot_range_type fps_score_choose_foot_range_type desc_range fps_score_range desc_vdw_threshold fps_score_vdw_threshold desc_es_threshold fps_score_es_threshold desc_hb_threshold fps_score_hb_threshold desc_use_remainder fps_score_use_remainder desc_score_rec_filename fps_score_receptor_filename desc_score_att_exp fps_score_vdw_att_exp desc_score_rep_exp fps_score_vdw_rep_exp desc_score_rep_rad_scale fps_score_vdw_rep_rad_scale desc_use_distance_dependent_dielectric fps_score_use_distance_dependent_dielectric desc_score_dielectric fps_score_dielectric desc_score_vdw_scale fps_score_vdw_fp_scale desc_score_es_scale fps_score_es_fp_scale desc_score_hb_scale fps_score_hb_fp_scale distance_tolerence distance_tolerance multigrid_vdw_norm_scale multigrid_score_vdw_norm_scale multigrid_es_norm_scale multigrid_score_es_norm_scale multigrid_vdw_euc_scale multigrid_score_vdw_euc_scale multigrid_es_euc_scale multigrid_score_es_euc_scale multigrid_vdw_cor_scale multigrid_score_vdw_cor_scale multigrid_es_cor_scale multigrid_score_es_cor_scale SASA_descriptor_score_primary SASA_score_primary SASA_descriptor_score_secondary SASA_score_secondary SASA_descriptor_score_rec_filename SASA_score_rec_filename Added: For Internal Energy Calculation: internal_energy_cutoff: [100.0] (): pruning_conformer_score_scaling_factor: [1.0] (): For Pharmacophore Matching Similarity Score: pharmacophore_score_primary [no] (yes no): pharmacophore_score_secondary [no] (yes no): fms_score_use_ref_mol2 [no] (yes no): fms_score_use_ref_txt [no] (yes no): fms_score_ref_mol2_filename [Ph4.mol2] (): fms_score_ref_txt_filename [Ph4.txt] (): fms_score_write_reference_pharmacophore_mol2 [no] (yes no): fms_score_write_reference_pharmacophore_txt [no] (yes no): fms_score_reference_output_mol2_filename [ref_ph4.mol2] (): fms_score_reference_output_txt_filename [ref_ph4.txt] (): fms_score_write_candidate_pharmacophore [no] (yes no): fms_score_candidate_output_filename [cad_ph4.mol2] (): fms_score_write_matched_pharmacophore [no] (yes no): fms_score_matched_output_filename [mat_ph4.mol2] (): fms_score_compare_type [overlap] (overlap compatible): fms_score_full_match [yes] (yes no): fms_score_match_rate_weight [5.0] (): fms_score_match_dist_cutoff [1.0] (): fms_score_match_proj_cutoff [0.7071] (): fms_score_max_score [20] (): For Descriptor Score: descriptor_score_primary [no] (yes no): descriptor_score_secondary [no] (yes no): descriptor_use_grid_score [yes] (yes no): descriptor_use_multigrid_score [yes] (yes no): descriptor_use_continuous_score [yes] (yes no): descriptor_use_footprint_similarity [yes] (yes no): descriptor_use_pharmacophore_score [no] (yes no): descriptor_use_tanimoto [no] (yes no): descriptor_use_hungarian [no] (yes no): descriptor_use_volume_overlap [no] (yes no): descriptor_grid_score_rep_rad_scale [1] (): descriptor_grid_score_vdw_scale [1] (): descriptor_grid_score_es_scale [1] (): descriptor_grid_score_grid_prefix [grid] (): descriptor_multigrid_score_rep_rad_scale [1] (): descriptor_multigrid_score_vdw_scale [1] (): descriptor_multigrid_score_es_scale [1] (): descriptor_multigrid_score_number_of_grids [20] (): descriptor_multigrid_score_grid_prefix0 [multigrid0] (): descriptor_multigrid_score_grid_prefix1 [multigrid1] (): descriptor_multigrid_score_grid_prefix2 [multigrid2] (): descriptor_multigrid_score_grid_prefix3 [multigrid3] (): descriptor_multigrid_score_grid_prefix4 [multigrid4] (): . . . descriptor_multigrid_score_grid_prefix17 [multigrid17] (): descriptor_multigrid_score_grid_prefix18 [multigrid18] (): descriptor_multigrid_score_grid_prefix19 [multigrid19] (): descriptor_multigrid_score_fp_ref_mol [yes] (yes no): descriptor_multigrid_score_footprint_ref [reference.mol2] (): descriptor_multigrid_score_use_euc [no] (yes no): descriptor_multigrid_score_vdw_euc_scale [1] (): descriptor_multigrid_score_es_euc_scale [1] (): descriptor_multigrid_score_use_norm_euc [yes] (yes no): descriptor_multigrid_score_vdw_norm_scale [10] (): descriptor_multigrid_score_es_norm_scale [10] (): descriptor_multigrid_score_use_cor [no] (yes no): descriptor_multigrid_score_vdw_cor_scale [-10] (): descriptor_multigrid_score_es_cor_scale [-10] (): descriptor_cont_score_rec_filename [receptor.mol2] (): descriptor_cont_score_att_exp [6] (): descriptor_cont_score_rep_exp [12] (): descriptor_cont_score_rep_rad_scale [1] (): descriptor_cont_score_use_dist_dep_dielectric [yes] (yes no): descriptor_cont_score_dielectric [4.0] (): descriptor_cont_score_vdw_scale [1] (): descriptor_cont_score_es_scale [1] (): descriptor_fps_score_use_footprint_reference_mol2 [no] (yes no): descriptor_fps_score_footprint_reference_mol2_filename [ligand_footprint.mol2] (): descriptor_fps_score_use_footprint_reference_txt [no] (yes no): descriptor_fps_score_footprint_reference_txt_filename [ligand_footprint.txt] (): descriptor_fps_score_foot_compare_type [Euclidean] (Pearson, Euclidean): descriptor_fps_score_normalize_foot [no] (yes no): descriptor_fps_score_foot_comp_all_residue [yes] (yes no): descriptor_fps_score_choose_foot_range_type [specify_range] (specify_range threshold): descriptor_fps_score_range [20-40,60-80] (): descriptor_fps_score_vdw_threshold [1] (): descriptor_fps_score_es_threshold [1] (): descriptor_fps_score_hb_threshold [0.5] (): descriptor_fps_score_use_remainder [yes] (yes no): descriptor_fps_score_receptor_filename [receptor.mol2] (): descriptor_fps_score_vdw_att_exp [6] (): descriptor_fps_score_vdw_rep_exp [12] (): descriptor_fps_score_vdw_rep_rad_scale [1] (): descriptor_fps_score_use_distance_dependent_dielectric [yes] (yes no): descriptor_fps_score_dielectric [4.0] (): descriptor_fps_score_vdw_fp_scale [1] (): descriptor_fps_score_es_fp_scale [1] (): descriptor_fps_score_hb_fp_scale [0] (): descriptor_fms_score_use_ref_mol2 [no] (yes no): descriptor_fms_score_use_ref_txt [no] (yes no): descriptor_fms_score_ref_mol2_filename [Ph4.mol2] (): descriptor_fms_score_ref_txt_filename [Ph4.txt] (): descriptor_fms_score_write_reference_ph4_mol2 [no] (yes no): descriptor_fms_score_write_reference_ph4_txt [no] (yes no): descriptor_fms_score_reference_output_mol2_filename [ref_ph4.mol2] (): descriptor_fms_score_reference_output_txt_filename [ref_ph4.txt] (): descriptor_fms_score_write_candidate_ph4 [no] (yes no): descriptor_fms_score_candidate_output_filename [cad_ph4.mol2] (): descriptor_fms_score_write_matched_ph4 [no] (yes no): descriptor_fms_score_matched_output_filename [mat_ph4.mol2] (): descriptor_fms_score_compare_type [overlap] (overlap compatible): descriptor_fms_score_full_match [yes] (yes no): descriptor_fms_score_match_rate_weight [5.0] (): descriptor_fms_score_match_dist_cutoff [1.0] (): descriptor_fms_score_match_proj_cutoff [0.7071] (): descriptor_fms_score_max_score [20] (): descriptor_fingerprint_ref_filename [fing_ref.mol2] (): descriptor_hms_score_ref_filename [hun_ref.mol2] (): descriptor_hms_score_matching_coeff [-5] (): descriptor_hms_score_rmsd_coeff [1] (): descriptor_volume_score_reference_mol2_filename [volume_reference.mol2] (): descriptor_volume_score_overlap_compute_method [analytical] (analytical grid): descriptor_volume_score_number_of_layers_in_one_dimension [30] (): descriptor_volume_score_maximum_grid_point_separation [0.3] (): descriptor_volume_score_write_points_cloud [no] (yes no]: descriptor_weight_grid_score [1] (): descriptor_weight_multigrid_score [1] (): descriptor_weight_cont_score [1] (): descriptor_weight_fps_score [1] (): descriptor_weight_pharmacophore_score [1] (): descriptor_weight_fingerprint_tanimoto [-1] (): descriptor_weight_hms_score [1] (): descriptor_weight_volume_overlap_score [-1] (): Removed: ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ FILE FORMAT CHANGES For DOCK: In mol2 files, residue numbers as opposed to literal "1"s are now emitted in the subst_id field of the @ATOM data record. Here is an example from install/test/mpi: 1 C1 23.6660 11.3403 56.9386 C.3 1 <0> -0.0897 to 1 C1 23.6660 11.3403 56.9386 C.3 7 <0> -0.0897 A new BILD file format is introduced, see section 4.3 in the manual. A new parameter file ph4.defn is included for pharmacophore score. For Multgrid Score: The grid arrays are no longer printed in the header of the mol2 but printed to the text file specified by the user. FOR DOCK Output Components: To increase the clarity of different output components a new naming convention has been adopted. Each output component has the prefix of the scoring function used to compute it. In addition the spacing of the output components has changed in the mol2 header file in order to accommodate addition of new output components Internal Energy: Int_energy Internal_energy_repulsive AMBER Score: Amber Score Amber_Score complex Amber_complex_energy receptor Amber_receptor_energy ligand Amber_ligand_energy Footprint Similarity Score: FPS_Score Footprint_Similarity_Score vdw FPS_vdw_energy es FPS_es_energy hbond FPS_num_hbond vdw+es FPS_vdw+es_energy vdw_fp FPS_vdw_fps es_fp FPS_es_fps hb_fp FPS_hb_fps vdw_fp_numres FPS_vdw_fp_numres es_fp_numres FPS_es_fp_numres hb_fp_numres FPS_hb_fp_numres Continuous Energy Score: Energy Score Continuous_Score vdw Continuous_vdw_energy es Continuous_es_energy Grid Score: Grid Score Grid_Score Grid_vdw Grid_vdw_energy Grid_es Grid_es_energy Contact Score: Contact Score Contact_Score DOCK3.5 Score: Energy Score Chemgrid_Score vdw Chemgrid_vdw_energy ele Chemgrid_es_energy polsol Chemgrid_polsol apolsol Chemgrid_apolsol MultiGrid Footprint Similarity Score: MultiGrid Score MultiGrid_Score MultiGrid_vdw MGS_vdw_energy MultiGrid_es MGS_es_energy vdwcor MGS_vdw_fps escor MGS_es_fps vdweuc MGS_vdw_fps eseuc MGS_es_fps vdwnorm MGS_vdw_fps esnorm MGS_es_fps Zou GB/SA score: GB/SA Score Zou_GBSA_Score vdw Zou_GBSA_vdw_energy gb Zou_GBSA_gb_energy sa Zou_GBSA_sa_energy del_SAS_hp Zou_GBSA_delta_SAS_hp_energy Hawkins GB/SA score: GB/SA Score Hawkins_GBSA_Score vdw Hawkins_GBSA_vdw_energy es Hawkins_GBSA_es_energy gb Hawkins_GBSA_gb_energy sa Hawkins_GBSA_sa_energy PB/SA score: PB/SA Score PBSA_Score vdw PBSA_vdw_energy pb PBSA_pb_energy sa PBSA_sa_energy Sasa Score: SASA Score SASA_Score com_sasa_lig_tot SASA_com_lig_sasa_tot lig_sasa_tot SASA_lig_sasa_tot com_sasa_lig_phobic SASA_com_lig_sasa_phobic lig_sasa_phobic SASA_lig_sasa_phobic com_sasa_lig_philic SASA_com_lig_sasa_philic lig_sasa_philic SASA_lig_sasa_philic com_sasa_lig_other SASA_com_lig_sasa_other lig_sasa_other SASA_lig_sasa_other The following output components have been removed from the mol2 header file. If necessary they can be reprinted in the mol2 file by uncommenting the old source code lines in src/dock/score_sasa.cpp. %_phobic_lig_buried %_lig_phobic_buried/tot_buried %_rec_phobic_buried/tot_buried rec_sasa_tot rec_sasa_phobic rec_sasa_philic rec_sasa_other com_sasa_tot com_sasa_phobic com_sasa_philic com_sasa_other com_sasa_tot_lig com_sasa_phobic_lig com_sasa_philic_lig com_sasa_other_lig com_sasa_tot_rec com_sasa_phobic_rec com_sasa_philiic_rec com_sasa_other_rec ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ RELEASE DATE April 2017 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ REFERENCES 1. Jiang, L.; Rizzo, R. C. Pharmacophore-Based Similarity Scoring for DOCK. J. Phys. Chem. B, 2015, 119 (3), 1083-1102.