Scoring Functions

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.

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

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

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:

1. The distance between HD and XA is less than or equal to 2.5 angstroms;
2. 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:

1. One can give a mol2 file containing a reference molecule, and footprints will be calculated.
2. One can pass a text file containing VDW, ES, and H-bond footprints.

There are different choices for selection of residues:

1. All residues.
2. 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.
3. Selected residues.

Note that for (2) and (3) the remaining residue interaction may be placed in a remainder value included in the footprint.