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 发展新的理论方法来计算这些影响， 的宏观介电模型，并应用这些和现有的方法 到蛋白质和小分子。在待使用的模型中，蛋白质是 作为浸入高介电溶剂中的低介电介质处理， 电势由泊松或泊松决定 玻尔兹曼方程方程组将用有限差分法求解 方法.将发展三种新的理论方法： 构象变化（这种类型的先前计算假设 刚性结构）;反吸附的结合;以及 随机分子动力学的宏观介电方法 通过计算反应场的方法。应用于问题 生物学意义和方法学测试案例包括： 静电对酶抑制剂结合自由能的贡献; 血红蛋白中阴离子吸附效应（阴离子玻尔效应）的测定;以及 氧化还原电位和电子转移重组的计算 小分子和修饰血红素蛋白中的能量。

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 dieletric 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 stochastic molecular dynamics methods through calculations of reaction fields.Applications to problems of biological interest and test cases for the methodology include: electrostatic contributions to enzyme-inhibitor binding free energy; calcu- lations of anion adsorption effects (anion Bohr effects) in hemoglobin; and calculations of redox potentials and electron transfer reorganization energies in small molecules and modified heme proteins.