THEORETICAL STUDIES OF PROTEIN ELECTROSTATICS

拟议研究的总体目的是提高我们的理解。 生物分子中的静电效应。具体目标是 为了开发新的理论方法来计算这些影响 宏观介电模型的上下文，并应用这些和 现有的方法可以用于蛋白质和小分子。在要创建的模型中 使用时，蛋白质被视为低介电介质，浸泡在 高介电性溶剂，其电势由 泊松或泊松-玻尔兹曼方程。这些方程将通过以下方式解出 有限差分法。三种新的理论方法论将是 已开发：包括构象变化(以前的计算 这种类型具有刚性结构)；并入反离子 吸附；以及宏观介电方法与 分子动力学和量子力学计算方法 反应场的大小。应用于生物学研究中的问题和 该方法的测试案例包括捕光蛋白质 细菌视紫红质与一类与细胞有关的磷酸酶蛋白 监管。

The general aim of the proposed research is to improve our understanding of electrostatic effects in biological molecules. The specific aims are to develop new theoretical methods of calculating these effects in the context of a macroscopic dielectric model, and to apply these and existing methods to proteins and small molecules. In the model to be used, the protein is treated as a low dielectric medium immersed in a high dielectric solvent, and the electric potential is determined by the Poisson or Poisson-Boltzmann equation. The equations will be solved by finite difference methods. Three new theoretical methodologies will be developed: inclusion of conformation variation (previous calculations of this type have assumed rigid structures); incorporation of counterion adsorption; and combination of the macroscopic dielectric method with molecular dynamics and quantum mechanical methods through calculations of reaction fields. Applications to problems of biological interest and test cases for the methodology include the light harvesting protein bacteriorhodopsin and a family of phosphatase proteins involved in cell regulation.