噬菌体T4溶菌酶溶液构象模拟中分子力场和水模型的选择

蛋白质在溶液中可能以不同构象的集合形式存在，不能用单一的静态结构来表示. 分子动力学模拟已成为对溶液中蛋白质构象进行采样的有用工具，但分子力场和水模型的选择是关键问题. 这项工作介绍了噬菌体T4溶菌酶的个例研究. 本文发现，使用经典的AMBER99SB力场和TIP4P水模型，分子动力学模拟不能很好地描述野生型噬菌体T4溶菌酶在微秒时间尺度上的铰链弯曲结构域运动. 其它新型力场和水模型的组合，如被称为RSFF2+的残基特异性力场和离散校正的水模型TIP4P-D，能够对噬菌体T4溶菌酶溶液构象进行合理的采样，与实验数据有良好的一致性. 这项工作为进一步研究噬菌体T4溶菌酶的溶液构象转变提供了分子力场和水模型的参考.

Choice of Force Fields and Water Models for Sampling Solution Conformations of Bacteriophage T4 Lysozyme

A protein may exist as an ensem-ble of different conformations in solution, which cannot be repre-sented by a single static structure. Molecular dy-namics (MD) simulation has become a useful tool for sampling protein conformations in solution, but force fields and water models are important issues. This work presents a case study of the bacteriophage T4 lysozyme (T4L). We have found that MD simulations using a classic AMBER99SB force field and TIP4P water model cannot well describe hinge-bending domain motion of the wild-type T4L at the timescale of one microsecond. Other combinations, such as a residue-speci c force eld called RSFF2+ and a dispersion-corrected water model TIP4P-D, are able to sample reasonable solution conformations of T4L, which are in good agreement with experimental data. This primary study may provide candidates of force fields and water models for further investigating conformational transition of T4L.