MODELING HYDROPHOBIC AND HYDROPHILLIC INTERACTIONS

分子模拟正在迅速成为化学和化学中的重要工具 生物化学。有用的力场，友好的分子力学和 分子动力学程序是可用的，这些方法起到了非常重要的作用 在计算机辅助分子设计(CAMD)中的重要作用。有一个很宽的 时间尺度的分离以及短程和长程作用力 系统。这项提议的一个主要目标是申请多次 最近在我的团队中发现的Scaling方法加速了 生物分子模拟。 除其他外，蛋白质折叠和膜的形成取决于 关于水分子如何相互作用以及如何与水分子相互作用 链分子上的化学基团。越来越明显的是，简单的 已在使用的固定电荷两体静电水势模型 在生物模拟和CAMD中忽略重要影响，并可能 高估了溶剂分离的疏水对而不是接触对。 这些模型也不能准确地描述离子水合作用。 这项提议的另一个重要目标是设计出准确的 水和更复杂的分子的潜在模型，允许原子 随着化学环境的变化而变化的电荷。这个 目标是能够对水的界面属性进行建模， 疏水效果，离子水合一体式精准 相容势能模型。建议的模型包含所有 当前两体静电模型中遗漏的重要效应 通常在模拟中使用。有了这个新的模型，我们建议研究 疏水聚集，水诱导的链折叠，胶束形成， 以及离子的溶剂化作用。 拟议的研究将提供新的方法和算法用于 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.