Experimental Benchmarks for Protein/Water Force Fields

蛋白质/水力场的实验基准

• 批准号: 6463392
• 负责人: Teresa L. Head-Gordon
• 金额: $ 24.88万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6463392
• 关键词: aminoacid; analytical method; atmospheric pressure; chemical hydration; chemical stability; chemical structure function; computer simulation; intermolecular interaction; lactalbumin; low angle X ray diffraction analysis; lysozyme; mathematics; model design /development; molecular dynamics; molecular site; neutron diffraction; physical model; protein folding; proteins; stoichiometry; structural biology; technology /technique development; temperature; thermodynamics; water; water solution

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.

描述（由申请人提供）：我们寻求对综合理论的支持 以及将推进我们的溶液散射实验的实验计划， 分子动力学模拟和理论分析专业知识，进一步 进入两种模型蛋白质的纯水和水合区域 系统和熔球蛋白。我们建议开展高质量 纯水去除的散射实验和适当的理论分析 从环境条件，并研究氨基酸单体水溶液 使用模拟和散射实验来确定自由能 多种单体和一些三聚氨基酸在水中的缔合。 实验确定的氨基酸单体溶剂化将得到扩展 通过考虑水合在稳定中的作用，对真实的蛋白质链进行分析 各种溶菌酶和α-乳清蛋白的熔球中间体。我们建议 模拟并进行标记的中子溶液散射实验 溶菌酶折叠类的天然形式和熔球形式 通过实验确定不同强度所产生的差异 天然和熔球下疏水核的结构组织 状况。蛋白质模拟质量的基准测试 潜在的经验力场自然地在模拟中得到解决， 这里提出的实验研究。