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

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Abstract/Contents

Abstract: 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 μs trajectories of the FiP35 WW domain (Shaw, D. E. et al. Science 2010, 330, 341346). 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 μs 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.

Type of resource	software, multimedia
Date created	2011

Related Publication	Lane, T. J., Bowman, G. R., Beauchamp, K., Voelz, V. A. & Pande, V. S. Markov State Model Reveals Folding and Functional Dynamics in Ultra-Long MD Trajectories. J. Am. Chem. Soc. 133, 18413–18419 (2011). Available at: http://pubs.acs.org/doi/abs/10.1021/ja207470h
Related Publication	Shaw, D. E. et al. Atomic-Level Characterization of the Structural Dynamics of Proteins. Science 330, 341–346 (2010). Available at: https://www.sciencemag.org/content/330/6002/341.abstract
Location	https://purl.stanford.edu/hk910vk1684

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Preferred Citation: Lane, T. J., Bowman, G. R., Beauchamp, K., Voelz, V. A. & Pande, V. S. (2011) Markov State Model Reveals Folding and Functional Dynamics in Ultra-Long MD Trajectories. Stanford Digital Repository. Available at http://purl.stanford.edu/hk910vk1684.

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