Difference between revisions of "Scoring Functions"
From Rizzo_Lab
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DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. | DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such. | ||
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== Continuous/DOCK Cartesian Energy Score== | == Continuous/DOCK Cartesian Energy Score== | ||
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|- | |- | ||
|} | |} | ||
| + | |||
| + | ==Grid-Based Score== | ||
| + | DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point. | ||
| + | [[Image:Mm-equation.png|450px|center]] | ||
| + | '''Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.''' | ||
| + | ===Grid Score Parameters=== | ||
| + | {| class="wikitable" | ||
| + | |+ | ||
| + | |- | ||
| + | ! Parameter | ||
| + | ! Description | ||
| + | ! Default Value | ||
| + | |- | ||
| + | | grid_score_primary | ||
| + | | Does the user want to perform grid-based energy scoring as the primary scoring function? || yes- | ||
| + | |- | ||
| + | | grid_score_rep_rad_scale | ||
| + | | Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on || 1.0 | ||
| + | |- | ||
| + | | grid_score_vdw_scale | ||
| + | | Scalar multiplier of the VDW energy component || 1 | ||
| + | |- | ||
| + | | grid_score_turn_off_vdw | ||
| + | | A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 || yes | ||
| + | |- | ||
| + | | grid_score_es_scale | ||
| + | | Flag to scale up or down the es portion of the scoring function when es scale is turned on || 1 | ||
| + | |- | ||
| + | | grid_score_turn_off_es | ||
| + | | A flag to turn off es portion of scoring function when grid score es scale = 0 || yes | ||
| + | |- | ||
| + | | grid_score_grid_prefix | ||
| + | | The prefix to the grid files containing the desired nrg/bmp grid || grid | ||
| + | |- | ||
| + | |} | ||
| + | |||
| + | ===Grid Score Output Components=== | ||
| + | These values will be printed in the header of the mol2 file post DOCK process. | ||
| + | |||
| + | {| class="wikitable" | ||
| + | |+ | ||
| + | |- | ||
| + | ! Output Component | ||
| + | ! Description | ||
| + | |- | ||
| + | | Grid_score | ||
| + | | Sum of the VDW and ES interactions | ||
| + | |- | ||
| + | | Grid_vdw_energy | ||
| + | | VDW interaction between the ligand grid | ||
| + | |- | ||
| + | | Grid_es_energy | ||
| + | | ES interaction betweent eh ligand and grid | ||
| + | |} | ||
| + | |||
==Footprint Similarity Score== | ==Footprint Similarity Score== | ||
Revision as of 13:15, 14 April 2020
DOCK uses several types of scoring functions to discriminate among orientations and molecules. Scoring is requested using the score_molecules parameter. A large portion of scoring functions can be called through descriptor score (but not all). Those with descriptor score functionality will be denoted as such.
Continuous/DOCK Cartesian Energy Score
Continuous scoring may be used to evaluate a ligand:receptor complex without the investment of a grid calculation, or to perform a more detailed calculation without the numerical approximation of the grid. Continuous score is implemented under Descriptor Score as well. Continuous score is a cartesian based score and can be combined with other Cartesian based scores with very little computational expense.
Continuous/DCE Score Parameters
| Parameter | Description | Default Value |
|---|---|---|
| continuous_score_primary | Does the user want to perform continuous non-grid scoring as the primary scoring function? | no |
| continuous_score_secondary | Does the user want to perform continuous non-grid scoring as the secondary scoring function? | no |
| cont_score_rec_filename | File that contains receptor coordinates | receptor.mol2 |
| cont_score_att_exp | VDW Lennard-Jones potential attractive exponent | 6 |
| cont_score_rep_exp | VDW Lennard-Jones potential repulsive exponent | 12 |
| cont_score_rep_rad_scale | Scalar multiplier of the radii for the repulsive portion of the vdw energy component only | 1.0 |
| cont_score_use_dist_dep_dielectric | Distance dependent dielectric switch | yes |
| cont_score_dielectric | Dielectric constant for the electrostatic term | |
| cont_score_vdw_scale | Scalar multiplier of vdw energy component | 1 |
| cont_score_vdw_scale | Flag to turn off vdw portion of the scoring function when cont_score_vdw_scale=0 | yes |
| cont_score_es_scale | Scalar multiplier of electrostatic energy component | 1.0 |
| cont_score_turn_off_es | Flag to turn off es portion of the scoring function when cont_score_es_scale = 0 | yes |
Continuous/DCE Score Output Components
| Output Component | Description |
|---|---|
| Continuous-score | sum of the van der Waals and electrostatic interactions |
| Continuous_vdw_energy | VDW interaction between ligand and receptor |
| Continuous_es_energy | ES interaction between the ligand and receptor |
Grid-Based Score
DOCK needs a fast scoring function to evaluate poses rapidly during growth. The energy grid is used for this. The grid stores the non-bonded Molecular Mechanics Potential of the receptor at each grid point.
Grid can be called under descriptor score but it is suggested to not mix grid-based and cartesian space as that will dramatically increase computing time.
Grid Score Parameters
| Parameter | Description | Default Value |
|---|---|---|
| grid_score_primary | Does the user want to perform grid-based energy scoring as the primary scoring function? | yes- |
| grid_score_rep_rad_scale | Scalar multiplier of the radii for the repulsive portion of the VDW energy component only when grid score is turned on | 1.0 |
| grid_score_vdw_scale | Scalar multiplier of the VDW energy component | 1 |
| grid_score_turn_off_vdw | A flag to turn off vdw portion of scoring function when grid score vdw scale = 0 | yes |
| grid_score_es_scale | Flag to scale up or down the es portion of the scoring function when es scale is turned on | 1 |
| grid_score_turn_off_es | A flag to turn off es portion of scoring function when grid score es scale = 0 | yes |
| grid_score_grid_prefix | The prefix to the grid files containing the desired nrg/bmp grid | grid |
Grid Score Output Components
These values will be printed in the header of the mol2 file post DOCK process.
| Output Component | Description |
|---|---|
| Grid_score | Sum of the VDW and ES interactions |
| Grid_vdw_energy | VDW interaction between the ligand grid |
| Grid_es_energy | ES interaction betweent eh ligand and grid |
Footprint Similarity Score
The Footprint Similarity Score is a scoring function that calculates intermolecular hydrogen bonds and footprint comparisons, in addition to standard intermolecular energies (VDW and ES).
Intermolecular Energies (VDW, ES) are calculated the same way as in Continuous Score.
A geometric definition of Hydrogen bonds is employed. We define 3 atoms XD, HD, and XA as the heavy atom donor, donated hydrogen, and heavy atom acceptor, respectively. There is a hydrogen bond present if the following two conditions are met:
- The distance between HD and XA is less than or equal to 2.5 angstroms;
- The angle defined by XD, HD, and XA is between 120 and 180 degrees.
Footprints are a per-residue decomposition of interactions between the ligand and the receptor. This can be performed for all three terms VDW, ES, HB. Two footprints can be compared in three ways: Standard Euclidean, Normalized Euclidean, Pearson Correlation.
Footprints are used to gauge how similar two poses or two molecules are to one-another. For applications to virtual screening applications a reference is required.
There are to choices for a reference:
- One can give a mol2 file containing a reference molecule, and footprints will be calculated.
- One can pass a text file containing VDW, ES, and H-bond footprints.
There are different choices for selection of residues:
- All residues.
- Residues chosen using a threshold (union of the sets of reference and pose). The VDW, ES, and HB footprints may have different residues chosen in this case.
- Selected residues.
Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.
Footprint Similarity Score can be called under Descriptor Score.
Footprint Similarity Score Parameters
| Parameter | Description | Default Value |
|---|---|---|
| footprint_similarity_score_primary | Flag to perform footprint scoring as the primary scoring function | no |
| footprint_similarity_score_secondary | Flag to perform footprint scoring as the secondary scoring function. | no |
| fps_score_use_footprint_reference_mol2 | Use a molecule to calculate footprint reference. | no |
| fps_score_footprint_reference_mol2_filename | Path to the reference mol2 file - only used when footprint reference mol2 is turned on. | ligand_footprint.mol2 |
| fps_score_use_footprint_reference_txt | Use a pre-calculated footprint reference in text format. | no |
| fps_score_footprint_reference_txt_filename | Path to the reference txt file - only used when footprint reference txt is turned on. | ligand_footprint.txt |
| fps_score_foot_compare_type | Footprint similarity calculation methods (Options: Euclidean, Pearson). If Pearson, the correlation coefficient as the metric to compare the footprints. When the value is 1 then there is perfect agreement between the two footprints. WHen the value is 0 then there is poor agreement between the two footprints. If Euclidean, the Euclidean distance as the metric to compare the footprints. When the value is 0 then there is perfect agreement btween the two footprints. As the agreement gets worse between the two footprints the value increases. | Euclidean |
| fps_score_normalize_foot | normalization is used only with Euclidean distance. | no |
| fps_score_foot_comp_all_residue | If yes all residues are used for calculating the footprint. | yes |
| fps_score_choose_foot_range_type | User can use to determine the type of the range of the footprint by either specifying a residue range or defining a threshold. If specify_range, the user chooses to use a residue range and all footprints will be evaluated only on this residue range. First residue id = 1 not 0. If threshold, the user chose to use a residue range that is defined by only residues that have magnitudes that exceed the specified thresholds. (Options: specify_range, threshold) | specify_range |
| fps_score_vdw_threshold | Specify threshold for van der Waals energy, when threshold is turned on. | 1 |
| fps_score_es_threshold | Specify threshold for electrostatic energy, when threshold is turned on. | 1 |
| fps_score_hb_threshold | specify threshold for hydrogen bonds (integers). 0.5 means that all none zeros are used, when threshold is turned on. | 0.5 |
| fps_score_use_remainder | Interaction remainder is all remaining residues not included individually | yes |
| fps_score_rec_filename | File that contains receptor coordinates | receptor.mol2 |
| fps_score_att_exp | VDW Lennard-Jones potential attractive exponent | 6 |
| fps_score_rep_exp | VDW Lennard-Jones potential repulsive exponent | 12 |
| fps_score_rep_rad_scale | Scalar multiplier of the radii for the repulsive portion of the VDW energy component ONLY | 1 |
| fps_score_use_distance_dependent_dielectric | Distance dependent dielectric switch | yes |
| fps_score_dielectric | Dielectric constant for electrostatic term | 4.0 |
| fps_score_vdw_scale | Scalar multiplier of vdw energy component | 1 |
| fps_score_es_scale | Scalar multiplier of es energy component | 1 |
| fps_score_hb_scale | Scalar multiplier of hb energy component | 0 |
| fps_score_internal_scale | Scalar multiplier of internal energy component | 0 |
| fps_score_fp_vwd_scale | Scalar multiplier of vdw footprint component | 0 |
| fps_score_fp_es_scale | Scalar multiplier of es footprint component | 0 |
| fps_score_fp_hb_scale | Scalar multiplier of hb footprint component | 0 |
Footprint Similarity Score Output Components
| Output Component | Description |
|---|---|
| Footprint_similarity_score | sum of the van der Waals, electostatic, and hbond footprint similarity scores |
| FPS_vdw_energy | VDW interaction between ligand and receptor |
| FPS_es_energy | ES interaction between the ligand and receptor |
| FPS_num_hbond | number of hydrogen bonds |
| FPS_vdw+es_energy | sum of the van der Waals and electrostatic components |
| FPS_vdw_fps | vdw footprint similarity score |
| FPS_es_fps | ES footprint similarity score |
| FPS_hb_fps | hbond footprint similarity score |
| FPS_vdw_fp_numres | number of residues in the receptor considered during the calculation |
| FPS_es_fp_numres | number of residues in the receptor considered during the calculation |
| FPS_hb_fp_numres | number of residues in the receptor considered during the calculation |
