Why the OPLS-AA Force Field Cannot Produce the β-Hairpin Structure of H1 Peptide in Solution When Comparing with the GROMOS 43A1 Force Field?
Why the OPLS-AA Force Field Cannot Produce the β-Hairpin Structure of H1 Peptide in Solution When Comparing with the GROMOS 43A1 Force Field?
复制标题
DOI：
10.1080/07391102.2011.10507403
复制
发表时间：
2011-12-01
影响因子：
4.4
通讯作者：
Wang, Jihua
中科院分区：
文献类型：
--
作者：
Cao, Zanxia;Liu, Lei;Wang, Jihua
力场与水模型的优化组合是提高不同类型蛋白质和多肽分子动力学模拟质量的关键问题。在这项工作中，已尝试探索的问题，通过研究H1肽使用四种不同的模型，基于不同的力场，水模型和静电方案。采用温度复制交换分子动力学模拟（T-REMD）研究了H1肽构象转变的驱动力，以及GROMOS 43 A1力场能使H1肽在溶液中形成β-发夹结构，而OPLS-AA力场却不能的原因.使用GROMOS 43 A1力场的模拟更倾向于采用β-发夹结构，这与其他几个模拟和实验证据吻合良好。然而，使用OPLS-AA力场的模拟与使用GROMOS 43 A1力场模拟的模拟有显著差异。结果表明，HI肽构象转变的驱动力是其疏水残基的溶剂暴露。然而，残余物-残余物相互作用和残余物-溶剂相互作用之间的微妙平衡被使用OPLS-AA力场破坏，这导致残余物-残余物接触的数量减少。对于使用OPLS-AA力场采样的所有构象，观察到疏水残基的类似溶剂暴露。对于疏水残基暴露于大量溶剂的H1肽，具有SPC水模型的GROMOS 43 A1力场可以提供更准确的结果。
The optimal combination of force field and water model is an essential problem that is able to increase molecular dynamics simulation quality for different types of proteins and peptides. In this work, an attempt has been made to explore the problem by studying H1 peptide using four different models based on different force fields, water models and electrostatic schemes. The driving force for HI peptide conformation transition and the reason why the OPLS-AA force field cannot produce the beta-hairpin structure of H1 peptide in solution while the GROMOS 43A1 force field can do were investigated by temperature replica exchange molecular dynamics simulation (T-REMD). The simulation using the GROMOS 43A1 force field preferred to adopt a beta-hairpin structure, which was in good agreement with the several other simulations and the experimental evidences. However, the simulation using the OPLS-AA force field has a significant difference from the simulations with the GROMOS 43A1 force field simulation. The results show that the driving force in HI peptide conformation transition is solvent exposure of its hydrophobic residues. However, the subtle balances between residue-residue interactions and residue-solvent interaction are disrupted by using the OPLS-AA force field, which induced the reduction in the number of residue-residue contact. Similar solvent exposure of the hydrophobic residues is observed for all the conformations sampled using the OPLS-AA force field. For H1 peptide which exhibits large solvent exposure of the hydrophobic residues, the GROMOS 43A1 force field with the SPC water model can provide more accurate results.