Exploration of conformational transition pathways from coarse-grained simulations

被引:24
作者
Sfriso, Pedro [1 ,2 ]
Hospital, Adam [1 ,2 ,3 ]
Emperador, Agusti [1 ,2 ]
Orozco, Modesto [1 ,2 ,3 ,4 ]
机构
[1] Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
[2] Joint IRB BSC Program Computat Biol, Barcelona 08028, Spain
[3] Univ Barcelona, Natl Inst Bioinformat, E-08028 Barcelona, Spain
[4] Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain
基金
欧洲研究理事会;
关键词
DISCRETE MOLECULAR-DYNAMICS; NORMAL-MODE ANALYSIS; ENERGY LANDSCAPES; MACROMOLECULAR MOTIONS; PROTEIN FLEXIBILITY; COMPUTER-SIMULATION; ADENYLATE KINASE; DATABASE; REFINEMENT; DNA;
D O I
10.1093/bioinformatics/btt324
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: A new algorithm to trace conformational transitions in proteins is presented. The method uses discrete molecular dynamics as engine to sample protein conformational space. A multiple minima Go-like potential energy function is used in combination with several enhancing sampling strategies, such as metadynamics, Maxwell Demon molecular dynamics and essential dynamics. The method, which shows an unprecedented computational efficiency, is able to trace a wide range of known experimental transitions. Contrary to simpler methods our strategy does not introduce distortions in the chemical structure of the protein and is able to reproduce well complex non-linear conformational transitions. The method, called GOdMD, can easily introduce additional restraints to the transition (presence of ligand, known intermediate, known maintained contacts, ... ) and is freely distributed to the community through the Spanish National Bioinformatics Institute (http://mmb.irbbarcelona.org/GOdMD).
引用
收藏
页码:1980 / 1986
页数:7
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