Hawkins GB/SA Score

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The Hawkins GB/SA score is an implementation of the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method originally described by (Srinivasan, et al. J. Am. Chem. Soc. 1998) and reviewed by (Kollman, et al. Acc. Chem. Res. 2000). This particular implementation of MM-GBSA uses the pairwise GB solvation model reported by Hawkins, Cramer and Truhlar (Hawkins, et al. Chem. Phys. Lett. 1995 , Hawkins, et al. J. Phys. Chem. 1996) with parameters described by Tsui and Case (Tsui, et al. Biopolymers 2001). Solvent Accessible Surface Areas (SA) are computed using a C++ implementation of the Amber8 "icosahedra" algorithm.

The total interaction between the ligand and receptor are represented by unscaled Coulombic and Lennard jones energy terms (MM) plus the change (delta) in solvation (GBSA) where deltaGBSA = GBSA complex - (GBSA receptor + GBSA ligand). For any given species GBSA = Gpolar ( GB energy) + Gnonpolar (SA*0.00542 + 0.92). Note that if inner and outer dielectric constants are set to 1 (gas-phase) and 80 (water-phase), then GBSA terms are formally equivalent to free energies of hydration that can be directly compared with experimental data and useful for evaluating the accuracy of different partial charge models (Rizzo et al. J. Chem. Theory. Comput. 2006).

The Hawkins GB/SA score was intended to be used for "single-point" calculations and the current implementation is quite slow if energy minimization is performed at the same time. However, an energy minimization is highly recommended prior to GBSA single-point calculations given that scores can be very sensitive to receptor-ligand geometry. Use of the -v2 flag will yield separate GBSA terms for each species (complex, receptor, and ligand) and also include raw icosahedra SA values in units of angstroms squared. This scoring method requires that the vdw_AMBER_parm99.defn file be specified which contains GB radii and scale parameters for each atom type.

NOTE: The following parameter definitions will use the format below:

       parameter_name [default] (value):

In some cases, parameters are only needed (questions will only be asked) if the parameter above is enforced. These parameters are indicated below by additional indentation.

Hawkins GB/SA Score Parameters

        * gbsa_hawkins_score_primary [no] (yes, no):
          #Flag to perform Hawkins GB/SA scoring as the primary scoring
        * gbsa_hawkins_score_secondary [no] (yes, no):
          #Flag to perform Hawkins GB/SA scoring as the secondary scoring
              o gbsa_hawkins_score_rec_filename [receptor.mol2] (string):
                #File that contains receptor coordinates
              o gbsa_hawkins_score_solvent_dielectric [78.5] (float):
                #Dielectric constant for solvent
              o gbsa_hawkins_score_salt_conc(M) [0.0] (float):
                #Salt concentration for solvent at Molar concentration
              o gbsa_hawkins_score_gb_offset [0.09] (float):
                #GB radius offset
              o gbsa_hawkins_score_cont_vdw_and_es [yes] (yes, no):
                #Flag to determine whether vdw and es values will be
                #calculated continuously or from a grid
                (if gbsa_hawkins_score_cont_vdw_and_es = yes)
                    + gbsa_hawkins_score_vdw_att_exp [6] (int):
                      #VDW Lennard-Jones potential attractive exponent
                    + gbsa_hawkins_score_vdw_att_exp [12] (int):
                      #VDW Lennard-Jones potential repulsive exponent

              (if gbsa_hawkins_score_cont_vdw_and_es = no)
                  o gbsa_hawkins_score_vdw_att_exp [6] (int):
                    #VDW Lennard-Jones potential attractive exponent
                  o gbsa_hawkins_score_vdw_att_exp [12] (int):
                    #VDW Lennard-Jones potential repulsive exponent