THEORETICAL STUDIES OF PROTEIN ELECTROSTATICS

拟议研究的总体目标是提高我们的理解 生物分子中的静电效应。具体目标是 开发新的理论方法来计算这些影响， 宏观介电模型的背景下，并应用这些和 蛋白质和小分子。在模型中， 使用时，将蛋白质作为低介电介质处理， 高介电溶剂，并且电势由 Poisson或Poisson-Boltzmann方程方程将通过以下方式求解： 有限差分法三种新的理论方法将是 开发：包括构象变化（以前的计算 这种类型已假定刚性结构）; 吸附;以及宏观介电方法与 分子动力学和量子力学方法通过计算 反应场。生物学问题的应用， 该方法的测试案例包括捕光蛋白 细菌视紫红质和一个磷酸酶蛋白家族参与细胞 调控

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.