Peptide loop-closure kinetics from microsecond molecular dynamics simulations in explicit solvent.
Peptide loop-closure kinetics from microsecond molecular dynamics simulations in explicit solvent.
复制标题
DOI：
10.1021/ja025789n
复制
发表时间：
2002-05
影响因子：
15
通讯作者：
In-Chul Yeh;G. Hummer
中科院分区：
文献类型：
--
作者：
In-Chul Yeh;G. Hummer
最近用色氨酸三联体猝灭法测量了几种多肽的端到端接触形成率(Lapidus等人。程序娜塔莉。阿卡德。SCI。美国2000、97、7220)。受这些实验的启发，我们在不同初始条件和力场的多个全原子显式溶剂分子动力学模拟中研究了两个不同长度的多肽Cys-(Ala-Gly-Gln)n-Trp(n=1，2)的闭合动力学。在150个模拟中，每个大约20 ns，我们收集了分别用Amber和CHARMM力场模拟的五肽的1.0和0.8微米的数据，以及分别用两个力场模拟的八肽的大约0.5微米的数据。这些广泛的模拟使我们能够以原子分辨率分析未折叠状态下的肽的动力学，从而探索蛋白质折叠的早期事件，并直接将分子动力学模拟与实验进行比较。计算得到的色氨酸三重态的寿命范围为50-100 ns，与实验测量结果一致。然而，端到端接触形成得更快，特征时间不到10 ns。这两个力场的接触形成率是相似的，尽管各自的多肽构象系综不同。
End-to-end contact formation rates of several peptides were recently measured by tryptophan triplet quenching (Lapidus et al. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 7220). Motivated by these experiments, we study loop-closure kinetics for two peptides of different lengths, Cys-(Ala-Gly-Gln)n-Trp (n = 1, 2), in multiple all-atom explicit-solvent molecular dynamics simulations with different initial conditions and force fields. In 150 simulations of approximately 20 ns each, we collect data covering 1.0 and 0.8 micros for the penta-peptide simulated with the AMBER and CHARMM force fields, respectively, and about 0.5 micros each with the two force fields for the octa-peptide. These extensive simulations allow us to analyze the dynamics of peptides in the unfolded state with atomic resolution, thus probing early events in protein folding, and to compare molecular dynamics simulations directly with experiment. The calculated lifetimes of the tryptophan triplet state are in the range of 50-100 ns, in agreement with experimental measurements. However, end-to-end contacts form more rapidly, with characteristic times less than 10 ns. The contact formation rates for the two force fields are similar despite differences in the respective ensembles of peptide conformations.