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Molecular simulation of multistate peptide dynamics: A comparison between microsecond timescale sampling and multiple shorter trajectories
Author(s) -
Monticelli Luca,
Sorin Eric J.,
Tieleman D. Peter,
Pande Vijay S.,
Colombo Giorgio
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20935
Subject(s) - microsecond , molecular dynamics , sampling (signal processing) , statistical physics , biological system , kinetics , chemistry , computer science , chemical physics , computational chemistry , physics , biology , filter (signal processing) , astronomy , computer vision , quantum mechanics
Molecular dynamics simulations of the RN24 peptide, which includes a diverse set of structurally heterogeneous states, are carried out in explicit solvent. Two approaches are employed and compared directly under identical simulation conditions. Specifically, we examine sampling by two individual long trajectories (microsecond timescale) and many shorter (MS) uncoupled trajectories. Statistical analysis of the structural properties indicates a qualitative agreement between these approaches. Microsecond timescale sampling gives large uncertainties on most structural metrics, while the shorter timescale of MS simulations results in slight structural memory for beta‐structure starting states. Additionally, MS sampling detects numerous transitions on a relatively short timescale that are not observed in microsecond sampling, while long simulations allow for detection of a few transitions on significantly longer timescales. A correlation between the complex free energy landscape and the kinetics of the equilibrium is highlighted by principal component analysis on both simulation sets. This report highlights the increased precision of the MS approach when studying the kinetics of complex conformational change, while revealing the complementary insight and qualitative agreement offered by far fewer individual simulations on significantly longer timescales. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008