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Prediction of protein–protein complexes using replica exchange with repulsive scaling
Author(s) -
Siebenmorgen Till,
Engelhard Michael,
Zacharias Martin
Publication year - 2020
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.26187
Subject(s) - replica , molecular dynamics , scaling , van der waals force , chemical physics , maxima and minima , intermolecular force , statistical physics , chemistry , force field (fiction) , computer science , computational chemistry , physics , molecule , geometry , mathematics , quantum mechanics , art , mathematical analysis , organic chemistry , visual arts
The realistic prediction of protein–protein complex structures is import to ultimately model the interaction of all proteins in a cell and for the design of new protein–protein interactions. In principle, molecular dynamics (MD) simulations allow one to follow the association process under realistic conditions including full partner flexibility and surrounding solvent. However, due to the many local binding energy minima at the surface of protein partners, MD simulations are frequently trapped for long times in transient association states. We have designed a replica‐exchange based scheme employing different levels of a repulsive biasing between partners in each replica simulation. The bias acts only on intermolecular interactions based on an increase in effective pairwise van der Waals radii (repulsive scaling (RS)‐REMD) without affecting interactions within each protein or with the solvent. For a set of five protein test cases (out of six) the RS‐REMD technique allowed the sampling of near‐native complex structures even when starting from the opposide site with respect to the native binding site for one partner. Using the same start structures and same computational demand regular MD simulations sampled near native complex structures only for one case. The method showed also improved results for the refinement of docked structures in the vicinity of the native binding geometry compared to regular MD refinement.