Theoretical Studies of Aqueous Solvation of Proteins

这里描述的研究是为了发展蛋白质的水溶液溶剂化理论。简单的连续溶剂模型不足以描述氢键、水偶极子取向以及仅涉及少数水层分离的相互作用等现象。该项目的三个主要目标是发展溶剂化的解析分子理论，利用这些理论开发在分子动力学模拟中处理溶剂效应的新方法，以及研究特定蛋白质Rubredosin的溶剂化。虽然直接的方法是将水分子包括在蛋白质的计算机模拟中，但随着蛋白质和其他分子的大小或数量增加，这变得不切实际。这里的方法是使用积分方程式理论来预测液体的分子结构，但计算量比模拟方法少得多。这些理论可以用来计算由于溶剂对蛋白质的净作用力。大分子的溶剂效应理论对于发展探索生物聚合物的结构、动力学和热力学的理论方法至关重要。这些理论可以应用于蛋白质的特定的、当前的问题包括折叠、酶-底物结合以及蛋白质内部和蛋白质之间的电子转移。

The research described here is to develop theories for aqueous solvation of proteins. Simple continuum solvent models are insufficient to describe phenomena such as hydrogen-bonding, orientation of water dipoles, and interactions involving separations of only a few water layers. The three main objectives of this project are to develop analytic molecular theories of solvation, to use these theories to develop new methods for treating solvent effects in molecular dynamics simulations, and to study the solvation of a specific protein, rubredoxin. While the straightforward approach is to include water molecules in computer simulations of proteins, this becomes impractical as the size or number of proteins and other molecules increases. The approach here is to employ integral equation theories which predict the molecular structure of liquids but with much less computation than simulation methods. These theories can be used to calculate the net forces on the protein due to the solvent. %%% Theories for solvent effects on macromolecules are crucial to developing theoretical methods to probe the structure, dynamics and thermodynamics of biopolymers. Specific, current problems for proteins to which these theories can be applied include folding, enzyme-substrate binding, and electron-transfer in and between proteins.