Biased coarse-grained molecular dynamics simulation approach for flexible fitting of X-ray structure into cryo electron microscopy maps.

TitleBiased coarse-grained molecular dynamics simulation approach for flexible fitting of X-ray structure into cryo electron microscopy maps.
Publication TypeJournal Article
Year of Publication2010
AuthorsGrubisic I, Shokhirev MN, Orzechowski M, Miyashita O, Tama F
JournalJ Struct Biol
Volume169
Issue1
Pagination95-105
Date Published2010 Jan
ISSN1095-8657
KeywordsCryoelectron Microscopy, Crystallography, X-Ray, Molecular Dynamics Simulation, Proteins
Abstract

Several approaches have been introduced to interpret, in terms of high-resolution structure, low-resolution structural data as obtained from cryo-EM. As conformational changes are often observed in biological molecules, these techniques need to take into account the flexibility of proteins. Flexibility has been described in terms of movement between rigid domains and between rigid secondary structure elements, which present some limitations for studying dynamical properties. Normal mode analysis has also been used, but is limited to medium resolution data. All-atom molecular dynamics fitting techniques are more appropriate to fit structures into higher-resolution data as full protein flexibility is considered, but are cumbersome in terms of computational time. Here, we introduce a coarse-grained approach; a Go-model was used to represent biological molecules, combined with biased molecular dynamics to reproduce accurately conformational transitions. Illustrative examples on simulated data are shown. Accurate fittings can be obtained for resolution ranging from 5 to 20A. The approach was also tested on experimental data of Elongation Factor G and Escherichia coli RNA polymerase, where its validity is compared to previous models obtained from different techniques. This comparison demonstrates that quantitative flexible techniques, as opposed to manual docking, need to be considered to interpret low-resolution data.

DOI10.1016/j.jsb.2009.09.010
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/19800974?dopt=Abstract
Alternate JournalJ. Struct. Biol.
PubMed ID19800974