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Reformulating the entropic contribution in molecular docking scoring functions
Author(s) -
Procacci Piero
Publication year - 2016
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.24397
Subject(s) - entropy (arrow of time) , statistical physics , virtual screening , chemistry , computer science , biological system , computational chemistry , thermodynamics , algorithm , physics , molecular dynamics , biology
We have derived, in the context of the Rigid Rotor Harmonic Approximation (RRHO), a general mass and Planck's constant h independent expression for the dissociation free energy in ligand–receptor systems, featuring a systematically (anti‐binding) additive negative entropic term depending on readily available ligand–receptor quantities. The proposed RRHO expression allows to straightforwardly compute the absolute standard dissociation free energy without resorting to expensive normal mode analysis or other dynamical matrix‐based techniques for evaluating the entropic contribution, hence providing an effective scoring function for assessing docking poses with no adjustable parameters. Our RRHO formula was tested on a set of 55 ligand–receptor systems obtaining correlation coefficients and unsigned mean errors comparable to or better than those obtained with computationally demanding techniques for the dissociation entropy assessment. The proposed compact reformulation of the RRHO entropy term could constitute the basis for new and more effective scoring functions in molecular docking‐based high‐throughput virtual screening for drug discovery. © 2016 Wiley Periodicals, Inc.