Experimental Benchmarks for Protein/Water Force Fields

描述（由申请人提供）：我们寻求支持的组合理论 和实验计划，将推进我们的解决方案散射实验， 分子动力学模拟和理论分析专业知识，进一步 进入纯水和水溶液水合两种模型蛋白质的领域 系统和熔融球蛋白。我们建议开展高质量的 纯水的散射实验和相应的理论分析 从环境条件下，并研究氨基酸单体水溶液 使用模拟和散射实验来确定 各种单体和某些三聚体氨基酸在水中的结合。 实验确定的氨基酸单体的溶剂化作用将得到扩展 真实的蛋白质链， 各种溶菌酶和α-乳白蛋白的熔融球中间体。我们提出 模拟和进行中子溶液散射实验标记 溶菌酶折叠类的天然和熔融小球形式， 通过实验确定由不同 在天然和熔融球下疏水核的结构组织 条件蛋白质模拟的基准， 在模拟中自然地解决了潜在的经验力场， 实验研究在此提出。

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.