On the characterization of protein native state ensembles.

Abstract:

:Describing and understanding the biological function of a protein requires a detailed structural and thermodynamic description of the protein's native state ensemble. Obtaining such a description often involves characterizing equilibrium fluctuations that occur beyond the nanosecond timescale. Capturing such fluctuations remains nontrivial even for very long molecular dynamics and Monte Carlo simulations. We propose a novel multiscale computational method to exhaustively characterize, in atomistic detail, the protein conformations constituting the native state with no inherent timescale limitations. Applications of this method to proteins of various folds and sizes show that thermodynamic observables measured as averages over the native state ensembles obtained by the method agree remarkably well with nuclear magnetic resonance data that span multiple timescales. By characterizing equilibrium fluctuations at atomistic detail over a broad range of timescales, from picoseconds to milliseconds, our method offers to complement current simulation techniques and wet-lab experiments and can impact our understanding and description of the relationship between protein flexibility and function.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Shehu A,Kavraki LE,Clementi C

doi

10.1529/biophysj.106.094409

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

1503-11

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(07)70959-1

journal_volume

92

pub_type

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