Open AccessToward a Unified Representation of Protein Structural Dynamics in Solution
Author(s) -
Phineus R. L. Markwick,
Guillaume Bouvignies,
Loïc Salmon,
J. Andrew McCammon,
Michaël Nilges,
Martin Blackledge
Publication year - 2009
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/ja907476w
Subject(s) - chemistry , protein dynamics , molecular dynamics , biological system , flexibility (engineering) , dynamics (music) , statistical physics , representation (politics) , sampling (signal processing) , constraint (computer aided design) , chemical physics , conformational ensembles , protein structure , computational chemistry , computer science , physics , mechanical engineering , biochemistry , statistics , mathematics , engineering , filter (signal processing) , politics , political science , acoustics , law , computer vision , biology
An atomic resolution description of protein flexibility is essential for understanding the role that structural dynamics play in biological processes. Despite the unique dependence of nuclear magnetic resonance (NMR) to motional averaging on different time scales, NMR-based protein structure determination often ignores the presence of dynamics, representing rapidly exchanging conformational equilibria in terms of a single static structure. In this study, we use the rich dynamic information encoded in experimental NMR parameters to develop a molecular and statistical mechanical characterization of the conformational behavior of proteins in solution. Critically, and in contrast to previously proposed techniques, we do not use empirical energy terms to restrain a conformational search, a procedure that can strongly perturb simulated dynamics in a nonpredictable way. Rather, we use accelerated molecular dynamic simulation to gradually increase the level of conformational sampling and to identify the appropriate level of sampling via direct comparison of unrestrained simulation with experimental data. This constraint-free approach thereby provides an atomic resolution free-energy weighted Boltzmann description of protein dynamics occurring on time scales over many orders of magnitude in the protein ubiquitin.