A network of conformational transitions in an unfolding process of HP-35 revealed by high-temperature MD simulation and a Markov state model

doi:10.1088/1674-1056/27/1/018701

Abstract An understanding of protein folding/unfolding processes has important implications for all biological processes, including protein degradation, protein translocation, aging, and diseases. All-atom molecular dynamics (MD) simulations are uniquely suitable for it because of their atomic level resolution and accuracy. However, limited by computational capabilities, nowadays even for small and fast-folding proteins, all-atom MD simulations of protein folding still presents a great challenge. An alternative way is to study unfolding process using MD simulations at high temperature. High temperature provides more energy to overcome energetic barriers to unfolding, and information obtained from studying unfolding can shed light on the mechanism of folding. In the present study, a 1000-ns MD simulation at high temperature (500 K) was performed to investigate the unfolding process of a small protein, chicken villin headpiece (HP-35). To infer the folding mechanism, a Markov state model was also built from our simulation, which maps out six macrostates during the folding/unfolding process as well as critical transitions between them, revealing the folding mechanism unambiguously.

Keywords: molecular dynamics simulation Markov state model folding/unfolding HP-35

Received: 09 July 2017
Revised: 01 October 2017
Accepted manuscript online:

PACS:	87.14.E-	(Proteins)
	87.15.ap	(Molecular dynamics simulation)
	87.15.Cc	(Folding: thermodynamics, statistical mechanics, models, and pathways)

Fund: Project supported by the National Natural Science Foundation of China (Grant Nos. 11175068 and 11474117) and the Self-determined Research Funds of CCNU from the Colleges Basic Research and Operation of MOE, China (Grant No. 230-20205170054).

Corresponding Authors: Kaifu Gao
E-mail: gaokaifu@mail.ccnu.edu.cn

Cite this article:

Dandan Shao(邵丹丹), Kaifu Gao(高恺夫) A network of conformational transitions in an unfolding process of HP-35 revealed by high-temperature MD simulation and a Markov state model 2018 Chin. Phys. B 27 018701

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A network of conformational transitions in an unfolding process of HP-35 revealed by high-temperature MD simulation and a Markov state model

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