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BioMed Research International
Volume 2017 (2017), Article ID 5760612, 17 pages
https://doi.org/10.1155/2017/5760612
Research Article

All-Atom Four-Body Knowledge-Based Statistical Potentials to Distinguish Native Protein Structures from Nonnative Folds

School of Systems Biology, George Mason University, 10900 University Blvd. MS 5B3, Manassas, VA 20110, USA

Correspondence should be addressed to Majid Masso

Received 27 June 2017; Revised 13 August 2017; Accepted 23 August 2017; Published 8 October 2017

Academic Editor: Rita Casadio

Copyright © 2017 Majid Masso. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Recent advances in understanding protein folding have benefitted from coarse-grained representations of protein structures. Empirical energy functions derived from these techniques occasionally succeed in distinguishing native structures from their corresponding ensembles of nonnative folds or decoys which display varying degrees of structural dissimilarity to the native proteins. Here we utilized atomic coordinates of single protein chains, comprising a large diverse training set, to develop and evaluate twelve all-atom four-body statistical potentials obtained by exploring alternative values for a pair of inherent parameters. Delaunay tessellation was performed on the atomic coordinates of each protein to objectively identify all quadruplets of interacting atoms, and atomic potentials were generated via statistical analysis of the data and implementation of the inverted Boltzmann principle. Our potentials were evaluated using benchmarking datasets from Decoys-‘R’-Us, and comparisons were made with twelve other physics- and knowledge-based potentials. Ranking 3rd, our best potential tied CHARMM19 and surpassed AMBER force field potentials. We illustrate how a generalized version of our potential can be used to empirically calculate binding energies for target-ligand complexes, using HIV-1 protease-inhibitor complexes for a practical application. The combined results suggest an accurate and efficient atomic four-body statistical potential for protein structure prediction and assessment.