College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, China.
Phys Chem Chem Phys. 2019 Aug 21;21(33):18219-18226. doi: 10.1039/c9cp01703h.
The villin headpiece subdomain (HP35) is a fast-folding protein with 35 residues and its folding pathways have been extensively studied experimentally and theoretically but remain controversial. While experiments showed that HP35 might have multiple folding pathways, most theoretical studies only found one major pathway, although a few theoretical studies revealed two. Here we report our results of molecular dynamics simulations of HP35 folding by using the newest AMBER ff14SB force field and show that HP35 has a novel folding pathway in addition to the two pathways shown previously. We also study the mechanism of determining the folding pathways and found that the dynamics of Helix2 may play a special role in the folding of HP35. Our results may be helpful to understand the folding mechanism of HP35 further.
villin 头部结构域（HP35）是一个由 35 个残基组成的快速折叠蛋白，其折叠途径已被广泛研究，但仍存在争议。虽然实验表明 HP35 可能有多种折叠途径，但大多数理论研究只发现了一种主要途径，尽管少数理论研究揭示了两种途径。在这里，我们报告了使用最新的 AMBER ff14SB 力场对 HP35 折叠的分子动力学模拟结果，表明 HP35 除了以前显示的两种途径外，还有一种新的折叠途径。我们还研究了确定折叠途径的机制，发现 Helix2 的动力学可能在 HP35 的折叠中起特殊作用。我们的结果可能有助于进一步了解 HP35 的折叠机制。
