MODELING HYDROPHOBIC AND HYDROPHILLIC INTERACTIONS

分子建模正迅速成为化学中的重要工具， 生物化学有用的力场，和友好的分子力学， 分子动力学程序是可用的，这些方法发挥了非常重要的作用。 计算机辅助分子设计（CAMD）。有各种 分离的时间尺度和短期和长期的力量在这些 系统. 该提案的一个主要目标是应用多时间 最近在我的小组中发现了一种方法， 生物分子模拟 蛋白质折叠和膜的形成，除了其他的事情， 关键在于水分子如何相互作用， 链分子上的化学基团。越来越明显的是， 固定电荷两体静电水势模型 在生物模拟和CAMD中忽略了重要的影响， 高估溶剂分离的疏水对而不是接触对。 这些模型也不能准确描述离子水合作用。 这项建议的另一个重要目标是， 水和更复杂分子的潜在模型， 电荷随化学环境的变化而变化。 的 目标是能够模拟水的界面性质， 疏水作用，离子水合准确地与一个自我- 一致性势模型 所提出的模型包含所有 当前两体静电模型中遗漏的重要效应 经常用于模拟。 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。 该研究将为以下领域提供新的方法和算法： 生物模拟

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.