MODELING HYDROPHOBIC AND HYDROPHILLIC INTERACTIONS

模拟疏水和亲水相互作用

• 批准号: 2181970
• 负责人: BRUCE J BERNE
• 金额: $ 19.38万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2181970
• 关键词: biological models; chemical hydration; chemical models; computer simulation; hydropathy; intermolecular interaction; micelles; molecular dynamics; molecular polarity; molecular shape; protein folding; water solution

Molecular modeling is fast becoming an important tool in chemistry and biochemistry. Useful force fields, and friendly molecular mechanics and molecular dynamics programs are available, and these methods play a very important role in computer aided molecular design(CAMD). There is a wide separation of time scales and both short and long range forces in these systems. A major objective of this proposal is to apply Multiple Time Scale Methods recently discovered in my group to the acceleration of biomolecular simulations. Protein folding and membrane formation, among other things, depend crucially on how water molecules interact with each other and with chemical groups on chain molecules. It is becoming clear that the simple fixed charge two-body electrostatic water potential models already in use in biological simulations and in CAMD ignore important effects, and may overestimate solvent separated hydrophobic pairs over contact pairs. These models also cannot describe ion hydration accurately. Another important objective of this proposal is to devise accurate potential models for water and more complex molecules that allow atomic charges to change in response to a changing chemical environment. The goal is to be able to model interfacial properties of water, the hydrophobic effect, and ionic hydration accurately with one self- consistent potential model. The proposed models contain all of the important effects left out in current two-body electrostatic models routinely used in simulations. With this new model we propose to study hydrophobic aggregation, water induced chain folding, micelle formation, and the solvation of ions. The proposed research will provide new methods and algorithms for use in biological simulations.

分子建模迅速成为化学和 生物化学。有用的力场，友好的分子力学和 分子动力学程序可用，这些方法效果非常 在计算机辅助分子设计（CAMD）中的重要作用。有一个宽阔的 时间尺度的分离以及它们中的短和远程力 系统。 该提案的主要目标是多次申请 最近在我的小组中发现的比例方法 生物分子模拟。 蛋白质折叠和膜形成，除其他外 至关重要的是水分子如何相互相互作用以及 链分子上的化学基团。很明显，简单 固定电荷已经使用的两体静电水势模型 在生物模拟和CAMD中，忽略了重要的影响，可以 高估溶剂将疏水对分离，而不是接触对。 这些模型也无法准确描述离子水合。 该提案的另一个重要目标是设计准确 水和更复杂的分子的潜在模型，允许原子 响应不断变化的化学环境的费用。 这 目标是能够建模水的界面特性 疏水作用和离子水合作用一个自我保湿 一致的潜在模型。 提出的模型包含所有 当前两体静电模型中留下的重要效果 通常用于模拟。 通过这个新模型，我们建议研究 疏水聚集，水诱导的链折叠，胶束形成， 和离子的溶剂化。 拟议的研究将提供新的方法和算法供 生物模拟。