The early stage of folding of villin headpiece subdomain observed in a 200-nanosecond fully solvated molecular dynamics simulation
The early stage of folding of villin headpiece subdomain observed in a 200-nanosecond fully solvated molecular dynamics simulation
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DOI：
10.1073/pnas.95.17.9897
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发表时间：
1998-08-18
影响因子：
11.1
通讯作者：
Kollman, PA
中科院分区：
文献类型：
--
作者：
Duan, Y;Wang, L;Kollman, PA
一种在并行计算机上实现经典分子动力学模拟的新方法使得能够对具有水的明确表示的蛋白质进行模拟，该蛋白质比之前报道的数量级长一个数量级，并且很快将使这种模拟能够进行到微秒时间范围。我们已经使用这种方法来研究villin头件子域的折叠，这是一种由三个螺旋组成的36个残基的小蛋白质，从展开结构到折叠结构。 熔球状态，具有天然结构的许多特征。溶剂化自由能、回转半径以及与天然 NR IR 结构的主链 rms 差异的时间发展表明，该过程可以看作是 60 纳秒的“爆发”阶段，随后是缓慢的“构象重新调整”阶段。我们发现疏水表面的掩埋主导了折叠过程的早期阶段，并且似乎是该阶段回转半径减小的主要驱动力。
A new approach in implementing classical molecular dynamics simulation for parallel computers has enabled a simulation to be carried out on a protein with explicit representation of water an order of magnitude longer than previously reported and will soon enable such simulations to be carried into the microsecond time range, We have used this approach to study the folding of the villin headpiece subdomain, a 36-residue small protein consisting of three helices, from an unfolded structure to a molten globule state, which has a number of features of the native structure. The time development of the solvation free energy, the radius of gyration, and the mainchain rms difference from the native NR IR structure showed that the process can be seen as a 60-nsec "burst" phase followed by a slow "conformational readjustment" phase. We found that the burial of the hydrophobic surface dominated the early phase of the folding process and appeared to be the primary driving force of the reduction in the radius of gyration in that phase.