中国物理B ›› 2018, Vol. 27 ›› Issue (1): 18701-018701.doi: 10.1088/1674-1056/27/1/018701

所属专题： SPECIAL TOPIC — Soft matter and biological physics

• SPECIAL TOPIC—Soft matter and biological physics • 上一篇    下一篇

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

Dandan Shao(邵丹丹), Kaifu Gao(高恺夫)   

  1. Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan 430079, China
  • 收稿日期:2017-07-09 修回日期:2017-10-01 出版日期:2018-01-05 发布日期:2018-01-05
  • 通讯作者: Kaifu Gao E-mail:gaokaifu@mail.ccnu.edu.cn
  • 基金资助:
    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).

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

Dandan Shao(邵丹丹), Kaifu Gao(高恺夫)   

  1. Institute of Biophysics and Department of Physics, Central China Normal University, Wuhan 430079, China
  • Received:2017-07-09 Revised:2017-10-01 Online:2018-01-05 Published:2018-01-05
  • Contact: Kaifu Gao E-mail:gaokaifu@mail.ccnu.edu.cn
  • Supported by:
    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).

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摘要： 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.

关键词: molecular dynamics simulation, Markov state model, folding/unfolding, HP-35

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.

Key words: molecular dynamics simulation, Markov state model, folding/unfolding, HP-35

中图分类号:  (Proteins)

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