The ideal scoring function for molecular docking is the binding free energy.  Unfortunately, most scoring functions are based on a single configuration of the complex and fail to account for entropy.  A recently developed binding free energy formalism, implicit ligand theory, is especially amenable to molecular docking.  Unlike other formalisms, implicit ligand theory allows receptor configurations to be sampled independently from the ligand, such that this expensive calculation only needs to be performed once.  Next, the binding potential of mean force of a ligand to each frozen receptor conformation is calculated.  Because interactions between the frozen receptor and ligand atoms can be precalculated on a grid, the binding potential of mean force may be calculated much more quickly than binding free energies.  This presentation will review implicit ligand theory, describe its implementation with an adaptively scaled grid, and highlight results on model protein-ligand systems.

Molecular docking scores based on implicit ligand theory, a rigorous formalism for binding free energies

245th National Meeting (2013)

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