Coarse-grain simulations on NMR conformational ensembles highlight functional residues in proteins.

TitleCoarse-grain simulations on NMR conformational ensembles highlight functional residues in proteins.
Publication TypeJournal Article
Year of Publication2019
AuthorsSacquin-Mora S
JournalJ R Soc Interface
Volume16
Issue156
Pagination20190075
Date Published2019 Jul 26
ISSN1742-5662
Abstract

Dynamics are a key feature of protein function, and this is especially true of gating residues, which occupy cavity or tunnel lining positions in the protein structure, and will reversibly switch between open and closed conformations in order to control the diffusion of small molecules within a protein's internal matrix. Earlier work on globins and hydrogenases have shown that these gating residues can be detected using a multiscale scheme combining all-atom classic molecular dynamics simulations and coarse-grain calculations of the resulting conformational ensemble mechanical properties. Here, we show that the structural variations observed in the conformational ensembles produced by NMR spectroscopy experiments are sufficient to induce noticeable mechanical changes in a protein, which in turn can be used to identify residues important for function and forming a mechanical nucleus in the protein core. This new approach, which combines experimental data and rapid coarse-grain calculations and no longer needs to resort to time-consuming all-atom simulations, was successfully applied to five different protein families.

DOI10.1098/rsif.2019.0075
Alternate JournalJ R Soc Interface
Citation Key2019|2061
PubMed ID31288649
PubMed Central IDPMC6685036