Theoretical Studies of Aqueous Solvation of Proteins

蛋白质水溶剂化的理论研究

• 批准号: 9506796
• 负责人: Toshiko Ichiye
• 金额: $ 26万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9506796&HistoricalAwards=false
• 关键词: Theoretical; Studies; Aqueous; Solvation; Proteins

9506796 Ichiye The development of theories of aqueous solvation of biological macromolecules is crucial to understanding their structure and function. This research will develop theories for macromolecular solvation and implement them into simulation algorithms and to study specific interactions of water and counterions with proteins. Simple continuum solvent models are insufficient to describe phenomena such as hydrogen bonding, local dielectric perturbations and phenomena involving separations of only a few water layers. To understand and model the molecular nature of solvation, the approach used here is the development of statistical mechanical integral equation theories. First, the previously proposed integral equation theory for solvation of globular molecules will be extended to proteins. To facilitate this, a new model of water for simulations will be developed, which is equivalent to TIP4P in structural properties but is three times faster than 3-site water models in Monte Carlo simulations. Without further development, this theory can then be used to predict the solvation of a given structure; e.g., a crystal or NMR structure of a protein. Second, this theory of aqueous solvation of macromolecules will be incorporated into dynamics simulation algorithms. Currently, addition of explicit solvent into a molecular dynamics simulation is the only simulation method to include the molecular nature of water, but it is very costly in computer resources. Several different methods of incorporating this theory are discussed. The final goal is incorporation of ionic strength effects into simulation methods. %%% The development of theories of aqueous solvation of biological macromolecules is crucial to understanding their structure and function. This research will develop theories for macromolecular solvation and calculations that can then be used to study specific interactions of water and counterions with proteins. This theory can be used to predict t he solvation of a given structure; e.g., a crystal or NMR structure of a protein. Second, this theory of aqueous solvation of macromolecules will be incorporated into dynamics simulation algorithms. The final goal is incorporation of ionic strength effects into simulation methods. ***

9506796 Ichiye生物大分子水溶剂化理论的发展对于理解它们的结构和功能至关重要。 本研究将发展大分子溶剂化理论，并将其应用于模拟算法，并研究水和反离子与蛋白质的特定相互作用。 简单的连续溶剂模型是不足以描述的现象，如氢键，局部介电扰动和现象，涉及分离只有几个水层。 为了理解和模拟溶剂化的分子本质，这里使用的方法是统计力学积分方程理论的发展。 首先，以前提出的球形分子溶剂化的积分方程理论将扩展到蛋白质。 为了促进这一点，将开发一种新的模拟水模型，它在结构特性上与TIP 4P相当，但在蒙特卡洛模拟中比3点水模型快三倍。 在没有进一步发展的情况下，该理论可以用于预测给定结构的溶剂化;例如，蛋白质的晶体或核磁共振结构。 其次，将大分子水溶剂化理论引入动力学模拟算法中。 目前，在分子动力学模拟中加入显式溶剂是唯一一种包含水分子性质的模拟方法，但它在计算机资源上非常昂贵。 几种不同的方法，将这一理论进行了讨论。 最终目标是将离子强度效应纳入模拟方法。 生物大分子水溶剂化理论的发展对于理解它们的结构和功能至关重要。 这项研究将发展大分子溶剂化和计算的理论，然后可以用来研究水和反离子与蛋白质的特定相互作用。 该理论可用于预测给定结构的溶剂化;例如，蛋白质的晶体或核磁共振结构。 其次，将大分子水溶剂化理论引入动力学模拟算法中。 最终目标是将离子强度效应纳入模拟方法。 ***