Defining Protein Electrostatic Recognition Processes
Abstract
A coupled computational and interactive computer graphic approach is used to seek to elucidate the nature of electrostatic forces controlling the interaction of stable, catalytic, and transient binding complexes, which are basic to biological recognition processes. For each of these three kinds of binding, a specific macromolecular system has been selected for study. For the stable complex between the enzyme lysozyme and an antilysozyme antibody one can determine the role of electrostatic forces in the specificity and efficiency of binding. For the catalytic binding of the R67 plasmid enzyme dihydrofolate reductase, one deduces the role of electrostatic forces in the functionally important binding of the dihydrofolate substrate and the NADPH cofactor. For the transient electron-transfer complex between plastocyanin and cytochrome c, we will predict critical residues and interaction area for the electron transfer interaction. The specific aims are to develop and apply 1) novel algorithms for rapid calculation of electrostatic interactions allowing local side chain mobility and conformational changes, and dealing explicitly with solvent and counter-ions 2) new types of models using interactive computer graphic representations made possible by coupling supercomputers to computer graphics, 3) comprehensive automatic docking methods based upon electrostatic fields, and 4) detailed characterization of mechanisms of functionally important electrostatic interaction for three protein systems, including testable predictions for each of the three general types of protein recognition. (JHD)
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 30, 1989
- Accession Number
- ADA215482
Entities
People
- Elizabeth D. Getzoff
- Victoria A. Roberts