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 Jjournal_title
Biophysical journalauthors
Shehu A,Kavraki LE,Clementi Cdoi
10.1529/biophysj.106.094409subject
Has Abstractpub_date
2007-03-01 00:00:00pages
1503-11issue
5eissn
0006-3495issn
1542-0086pii
S0006-3495(07)70959-1journal_volume
92pub_type
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