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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29GM045607-01
Application #
3468367
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1991-01-01
Project End
1991-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037