Experimental Benchmarks for Protein/Water Force Fields

描述(由申请者提供)：我们寻求对综合理论的支持 和实验计划，这将推进我们的溶液散射实验， 分子动力学模拟和理论分析专业知识，进一步 进入纯水和水合两个模型蛋白质的领域 系统和熔化的球状蛋白质。我们建议进行高质量的 纯净水的散射实验及相应的理论分析 从环境条件，研究氨基酸单体水溶液 利用模拟和散射实验确定分子的自由能 水中各种单体和一些三聚体氨基酸的缔合。 实验确定的氨基酸单体的溶剂化将延长。 考虑水化作用对真实蛋白质链的稳定作用 各种溶菌酶和α-乳清蛋白的熔融小球中间体。我们建议 模拟和执行标记的中子溶液散射实验 溶菌酶的天然形态和熔融球状形态均可折叠成 通过实验确定由不同的 天然球体和熔融球体下疏水核心的结构组织 条件。对蛋白质模拟的质量进行分类 基本的经验力场在模拟中自然地被处理，并且 这里提出了实验研究的建议。

DESCRIPTION (provided by applicant): We seek support for a combined theoretical and experimental program that will advance our solution scattering experiments, molecular dynamics simulations, and theoretical analysis expertise, further into the area of pure water and aqueous hydration for both model protein systems and for molten globule proteins. We propose to conduct high quality scattering experiments and appropriate theoretical analysis on pure water away from ambient conditions, and to study aqueous amino acid monomer solutions using simulations and scattering experiments to determine the free energy of association of a variety of monomeric and some trimeric amino acids in water. The experimentally determined solvation of amino acid monomers will be extended to real protein chains by considering the role of hydration in stabilizing molten globule intermediates of various lysozymes and a-lactalbumin. We propose to simulate and perform neutron solution scattering experiments on labeled forms of both the native and molten globule forms of the lysozyme fold class to experimentally determine differences in intensity that arise from different structural organization of the hydrophobic core under native and molten globule conditions. The benchinarking of protein simulations as to the quality of the underlying empirical force fields is naturally addressed in the simulation and experimental research proposed here.