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

作者：Shao, Dandan; Gao, Kaifu^*

来源：Chinese Physics B, 2018, 27(1): 018701.

DOI：10.1088/1674-1056/27/1/018701

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

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.

• 出版日期2018-1
• 单位华中师范大学