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Refinement of protein‐protein complexes in contact map space with metadynamics simulations
Author(s) -
Pfeiffenberger Erik,
Bates Paul A.
Publication year - 2019
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25612
Subject(s) - metadynamics , curse of dimensionality , docking (animal) , molecular dynamics , energy landscape , computer science , snapshot (computer storage) , surface protein , searching the conformational space for docking , algorithm , protein structure prediction , protein structure , biological system , statistical physics , chemistry , computational chemistry , physics , artificial intelligence , thermodynamics , biology , medicine , nursing , virology , operating system , biochemistry
Abstract Accurate protein‐protein complex prediction, to atomic detail, is a challenging problem. For flexible docking cases, current state‐of‐the‐art docking methods are limited in their ability to exhaustively search the high dimensionality of the problem space. In this study, to obtain more accurate models, an investigation into the local optimization of initial docked solutions is presented with respect to a reference crystal structure. We show how physics‐based refinement of protein‐protein complexes in contact map space (CMS), within a metadynamics protocol, can be performed. The method uses 5 times replicated 10 ns simulations for sampling and ranks the generated conformational snapshots with ZRANK to identify an ensemble of n snapshots for final model building. Furthermore, we investigated whether the reconstructed free energy surface (FES), or a combination of both FES and ZRANK, referred to as CS α , can help to reduce snapshot ranking error.