Consensus modes, a robust description of protein collective motions from multiple-minima normal mode analysis - Application to the HIV-1 protease

Paulo Ricardo Batista, Charles Herbert Robert, Jean Didier Maréchal, Meriam Ben Hamida-Rebaï, Pedro Geraldo Pascutti, Paulo Mascarello Bisch, David Perahia

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

Protein flexibility is essential for enzymatic function, ligand binding, and protein-protein or protein-nucleic acid interactions. Normal mode analysis has increasingly been shown to be well suited for studying such flexibility, as it can be used to identify favorable structural deformations that correspond to functional motions. However, normal modes are strictly relevant to a single structure, reflecting a particular minimum on a complex energy surface, and are thus susceptible to artifacts. We describe a new theoretical framework for determining "consensus" normal modes from a set of related structures, such as those issuing from a short molecular dynamics simulation. This approach is more robust than standard normal mode analysis, and provides higher collectivity and symmetry properties. In an application to HIV-1 protease, the low-frequency consensus modes describe biologically relevant motions including flap opening and closing that can be used in interpreting structural changes accompanying the binding of widely differing inhibitors. © 2010 the Owner Societies.
Original languageEnglish
Pages (from-to)2850-2859
JournalPhysical Chemistry Chemical Physics
Volume12
Issue number12
DOIs
Publication statusPublished - 19 Mar 2010

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