The influence of different treatments of electrostatic interactions on the thermodynamics of folding of peptides
The influence of different treatments of electrostatic interactions on the thermodynamics of folding of peptides
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DOI：
10.1021/jp051325a
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发表时间：
2005-11-17
影响因子：
3.3
通讯作者：
Shea, JE
中科院分区：
文献类型：
--
作者：
Baumketner, A;Shea, JE
采用分子交换动力学模拟方法研究了不同静电处理对小β-发夹形成肽的结构和热力学的影响。三种不同的静电方案被认为是：定期截止，广义反应场（GRF），粒子网格埃瓦尔德（PME），与肽建模使用OPLS/AA全原子力场与明确的TIP 3 P水。GRF和PME方法都得到了与实验一致的结果，自由能表面显示出对应于天然β-发夹结构的单个最小值。相比之下，使用直线截止导致对应于非发夹构象的额外局部最小值的群体，所述非发夹构象在低温下与天然β-发夹的形成竞争。这个额外的最小值在传统的恒温分子动力学模拟中运行几纳秒是不明显的。这一结果指出，迫切需要仔细采样的构象空间，以评估质量的不同数值处理的长程力。虽然出现了差异的性质的未折叠状态填充使用PME和GRF的方法，模拟β-发夹形成肽和两个额外的控制肽表明，GRF处理静电提供了一个令人满意的折衷的准确性和计算速度之间的低能量构象的识别。基于GRF的方法作为一种可行的手段出现，用于处理使用PME方法进行模拟的成本过高的大型生物系统。
Replica exchange molecular dynamics simulations were performed to investigate the effects of different electrostatic treatments on the structure and thermodynamics of a small beta-hairpin forming peptide. Three different electrostatic schemes were considered: regular cutoffs, generalized reaction field (GRF), and particle mesh Ewald (PME), with the peptide modeled using OPLS/AA all-atom force field with explicit TIP3P water. Both the GRF and PME methods yielded results consistent with experiment, with free energy surfaces displaying a single minimum corresponding to the native beta-hairpin structure. In contrast, use of straight cutoffs led to the population of an additional local minimum corresponding to nonhairpin conformations that compete with the formation of the native beta-hairpin at low temperatures. This extra minimum would not be apparent in conventional constant-temperature molecular dynamics simulations run for a few nanoseconds. This result points to the critical need of careful sampling of conformational space to assess the quality of different numerical treatments of long-range forces. While differences emerged in the nature of the unfolded states populated using PME and GRF approaches, simulations on the beta-hairpin forming peptide and on two additional control peptides indicate that the GRF treatment of electrostatics offers a satisfactory compromise between accuracy and computational speed for the identification of low-energy conformations. A GRF-based approach emerges as a viable means for treating larger biological systems that would be prohibitively costly to simulate using PME methods.