Scoring functions physical based

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. 

As mean-force potentials become increasingly accurate, they will serve as a valuable tool for structure-based drug design. Detailed analysis of the mean-force potentials will provide insightful hints on how to improve other physics-based scoring functions. Mean-force potentials that perform well on binding mode predictions may also be implemented for molecular dynamics simulations of protein-ligand interactions. 

Physics-based all-atom molecular mechanics force fields have not been generally considered practical for fold detection because they are parameterized on small molecule data rather than on proteins directly the level of atomic detail contained in these models is considered poorly matched to the fold detection problem with respect to both accuracy and computational cost. Recent studies have shown, however, that a scoring function based on the potential energy from an all-atom molecular mechanics force field can recognize native protein conformations among a set of decoys as well as the best available knowledge-based scoring functions [6]. 

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