ELECTROSTATICS IN CHEMISTRY, BIOCHEMISTRY AND DRUG DEVELOPMENT (SPHERICAL CHARGE DENSITY, PROTEINS, CATION PI, ALZHEIMER'S DISEASE).

摘要

Proteins are important biomolecules responsible for numerous biological functions. Electrostatic interactions within and between protein molecules confer stability and help to define protein secondary and tertiary structure. Computational studies on biological systems are made possible by molecular mechanics. Electrostatic interactions are significant in biomolecules and as such, molecular simulations must incorporate an accurate description of these interactions. In molecular simulations, the charges in a molecule are treated as atom-centered, fixed point charges. This fixing of point charges in the field of moving nuclei is anti-Born-Oppenheimer. This treatment is not adequate, as electrons are quantum particles. This dissertation presents the development of a spherical charge density model to be used to treat electrostatics in molecular mechanics.; Another facet of electrostatic interactions is presented in this research. The focus is shifted to electrostatic interactions in proteins. The existence of cation-{dollar}pi{dollar} and anion-{dollar}pi{dollar} interactions between the side chains of proteins were studied by searching the Brookhaven Protein Data Bank (PDB). The nature and prevalence of these interactions are presented. The application of cation-{dollar}pi{dollar} interactions in the development of a drug for treating Alzheimer's disease is also presented.