Markov State Model Reveals Folding and Functional Dynamics in Ultra-Long MD Trajectories

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• 作者：Thomas J. Lane ; Gregory R. Bowman ; Kyle Beauchamp ; Vincent A. Voelz ; Vijay S. Pande
• 刊名：Journal of the American Chemical Society
• 出版年：2011
• 出版时间：November 16, 2011
• 年：2011
• 卷：133
• 期：45
• 页码：18413-18419
• 全文大小：1095K
• 年卷期：v.133,no.45(November 16, 2011)
• ISSN：1520-5126

文摘

Two strategies have been recently employed to push molecular simulation to long, biologically relevant time scales: projection-based analysis of results from specialized hardware producing a small number of ultralong trajectories and the statistical interpretation of massive parallel sampling performed with Markov state models (MSMs). Here, we assess the MSM as an analysis method by constructing a Markov model from ultralong trajectories, specifically two previously reported 100 渭s trajectories of the FiP35 WW domain (Shaw, D. E. Science 2010, 330, 341鈭?46). We find that the MSM approach yields novel insights. It discovers new statistically significant folding pathways, in which either beta-hairpin of the WW domain can form first. The rates of this process approach experimental values in a direct quantitative comparison (time scales of 5.0 渭s and 100 ns), within a factor of 2. Finally, the hub-like topology of the MSM and identification of a holo conformation predicts how WW domains may function through a conformational selection mechanism.