Tulip P R, Bates S P
Scottish Universities Physics Alliance (SUPA), School of Physics and Astronomy, The University of Edinburgh, Mayfield Road, Edinburgh EH9 3JZ, United Kingdom.
J Chem Phys. 2009 Jul 7;131(1):015103. doi: 10.1063/1.3160682.
We investigate the structure of the glycyl-l-alanine dipeptide in aqueous solution at a 1:20 peptide:water concentration via classical, atomistic molecular dynamics simulations using the CHARMM22 force field, and compare to recent neutron diffraction data [S. E. McLain, A. K. Soper, and A. Watts, Eur. Biophys. J. 37, 647 (2008); S. E. McLain, A. K. Soper, I. Diadone, J. C. Smith, and A. Watts, Angew. Chem. Int. Ed. 47, 9059 (2008)]. Comparison between simulations and experiments is made using the static structure factor S(Q). The effect of water model (TIP3P, TIP4P, and SPC/E) upon the solution structure is investigated. Agreement between experiment and simulation is generally good across the entire Q range, although some model-dependent variation is observed, particularly in the predicted intensities of features in S(Q). Peptide aggregation is found to be driven by "hydrophilic" (often bifurcated) hydrogen bonds formed between carboxy and amine functional groups, although simulations suggest that the degree of aggregation is less than that observed experimentally. It is found that hydrophobic association is not significant, with hydrophobic hydration being preferred to association. Detailed examination of the solute structural motifs reveals the existence of bifurcated motifs that are suggested to be an artifact of the CHARMM force field, and may imply that classical force fields provide a flawed structural and dynamical description of such molecular fluids. Investigation of the water structure reveals the presence of an electrostrictive effect which manifests itself as an increase in the number of interstitial molecules in the water second coordination shell, in contradiction to suggestions that this phenomenon arises owing to hydrogen bond bending. Detailed analysis based upon two-dimensional distribution functions suggests an intimate link between the phenomenon of electrostriction and the behavior of water under high-pressure compression. We find the magnitude of the electrostrictive effect inferred from the neutron diffraction data to be greater than that found in the simulations. Investigation of the solvation structure suggests that the CHARMM force field overhydrates the terminal carboxy group, and that this overhydration is accompanied by the presence of bifurcated hydrogen bonds.
我们通过使用CHARMM22力场的经典原子分子动力学模拟，研究了在肽与水浓度为1:20的水溶液中甘氨酰-L-丙氨酸二肽的结构，并与最近的中子衍射数据进行了比较[S. E. McLain, A. K. Soper, and A. Watts, Eur. Biophys. J. 37, 647 (2008); S. E. McLain, A. K. Soper, I. Diadone, J. C. Smith, and A. Watts, Angew. Chem. Int. Ed. 47, 9059 (2008)]。使用静态结构因子S(Q)对模拟结果与实验数据进行了比较。研究了水模型（TIP3P、TIP4P和SPC/E）对溶液结构的影响。尽管观察到一些与模型相关的变化，特别是在S(Q)中特征峰的预测强度方面，但在整个Q范围内，实验与模拟之间的一致性总体良好。发现肽聚集是由羧基和胺官能团之间形成的“亲水”（通常是分叉的）氢键驱动的，尽管模拟表明聚集程度低于实验观察到的程度。发现疏水缔合并不显著，疏水水合比缔合更受青睐。对溶质结构基序的详细研究揭示了分叉基序的存在，这被认为是CHARMM力场的一个假象，可能意味着经典力场对这种分子流体提供了有缺陷的结构和动力学描述。对水结构的研究揭示了电致伸缩效应的存在，其表现为水的第二配位层中间隙分子数量的增加，这与认为这种现象是由于氢键弯曲引起的观点相矛盾。基于二维分布函数的详细分析表明，电致伸缩现象与高压压缩下水的行为之间存在密切联系。我们发现从中子衍射数据推断出的电致伸缩效应的大小大于模拟中发现的大小。对溶剂化结构的研究表明，CHARMM力场使末端羧基过度水合，并且这种过度水合伴随着分叉氢键的存在。
