Nolde D E, Arseniev A S, Vergoten G, Efremov R G
Université des Sciences et Technologies de Lille, Centre de Recherches et d'Etudes en Simulations et Modélisation Moléculaires (CRESIMM), Villeneuve d'Ascq, France.
J Biomol Struct Dyn. 1997 Aug;15(1):1-18. doi: 10.1080/07391102.1997.10508940.
Several sets of atomic solvation parameters imitating: (i) nonpolar environment of hydrocarbon core of a membrane, (ii) aqueous solution, and (iii) weakly-polar solvents have been developed. The parameters have been incorporated into the ECEPP/2 and CHARMM force fields and employed in non-restrained Monte Carlo and molecular dynamics simulations of membrane-spanning alpha-helical peptides (segment A of bacteriorhodopsin, melittin). Through these simulations, the structure and energetics of the helices have been examined as a function of the solvation term in the potential energy function. For the peptides under study, the set (i) of atomic solvation parameters reveals good retention of the alpha-helical conformation. By contrast, the simulations in vacuum or with the parameters imitating a polar solvent (sets (ii) or (iii)) show fast helix destabilization and tight packing of the structure accompanied by significant decreasing of the surface area accessible to solvent. Increased helical propensity for amino acid residues, population of side-chain rotamers as well as hydrogen-bonding pattern in nonpolar membrane-like environment agree well with available experimental and computational data. The problems related to further applications of the membrane-mimicking sets of atomic solvation parameters to simulations of membrane proteins and peptides are addressed.
(i) 膜的烃类核心的非极性环境，(ii) 水溶液，以及 (iii) 弱极性溶剂。这些参数已被纳入ECEPP/2和CHARMM力场，并用于跨膜α-螺旋肽（细菌视紫红质的A段、蜂毒素）的无约束蒙特卡罗和分子动力学模拟。通过这些模拟，研究了螺旋的结构和能量学作为势能函数中溶剂化项的函数。对于所研究的肽，原子溶剂化参数集 (i) 显示出α-螺旋构象的良好保留。相比之下，在真空中或使用模拟极性溶剂的参数（集 (ii) 或 (iii)）进行的模拟显示螺旋快速失稳以及结构紧密堆积，同时溶剂可及表面积显著减小。在非极性膜状环境中，氨基酸残基的螺旋倾向增加、侧链旋转异构体的数量以及氢键模式与现有的实验和计算数据非常吻合。还讨论了与将模拟膜的原子溶剂化参数集进一步应用于膜蛋白和肽的模拟相关的问题。
