THEORETICAL STUDIES OF PROTEIN ELECTROSTATICS

蛋白质静电的理论研究

• 批准号: 3468367
• 负责人: DONALD E. BASHFORD
• 金额: $ 9.75万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3468367
• 关键词: Bohr effect; charge transfer complex; computer program /software; conformation; coulometry; dielectric property; electrical potential; enzyme inhibitors; heme; hemoglobin; intermolecular interaction; ionic bond; ionic strengths; ionization constant; lysozyme; mathematical model; molecular dynamics; molecular polarity; myoglobin; oxidation reduction reaction; thermolysin

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.

拟议研究的总体目的是提高我们的认识