Force field-based scoring functions

DOCK Automated docking program with incremental construction and random search algorithm and force field-based scoring function... 

Force-field-based scoring functions use arbitrary empirical estimates of interaction energies obtained by molecular mechanics energy functions. This simple approximation, which takes into account only enthalpic contribution often correlates well with the experiment. Solvent effects are described by atom-based solvation parameters, which are computed for the surface of both ligand and receptor which is buried upon complexation. DOCK-chemical27 and CHARMm scoring functions represent this class. 

Force field-based scoring functions are based on the nonbonded terms of a classical molecular mechanics force field (e.g.. Amber and CHARMm). A Lennard-Jones potential describes van der Waals interactions, whereas the Coulomb energy describes the electrostatic components of the interactions. The nonbonded interaction energy takes the following form ... 

In a similar fashion, Catana and Stouten [143] developed multiple functions based on QXP protein-ligand interaction terms [112]. The concept was also applied for improving a force field-based scoring function for CDK-2 using short MD simulations based on quantum-refined force fields [144]. Here, the statistical analysis of... 

Three main classes of fast scoring functions can be distinguished force field-based methods, empirical scoring functions, and knowledge-based methods. The following sections are dedicated to a separate discussion of each method. 

However, the free energy of binding is a state function so, in a strict physical sense, additivity is not allowed. These scoring functions at low computational cost are suitable for the calculation of an estimation of the binding free energy. Three main classes can be separated force field-based methods, empirical methods, and knowledge-based methods. 

Another approach based on statistical analysis of residue-specific protein-ligand interaction terms is named TScore [138[. Here, individual protein-ligand interactions are evaluated for each residue within 8 A around the ligand. Force field-based descriptors are replaced by Chemscore [96] and PLP [139] terms for hydrogen bonds, lipophilicity, and steric contact. Its application to a series of factor Xa inhibitors resulted in a predictive tailored scoring function vdth 52 selected descriptors after PLS analysis q = 0.(>4, r = 0.83). This concept allows a visual interpretation of... 

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