Defining Protein Electrostatic Recognition Processes
Abstract
The objective of this proposal is to elucidate the nature of electrostatic forces controlling protein recognition processes by using a tightly coupled computational and interactive computer graphics approach. We developed the TURNIP program to determine the most favorable precollision orientations for two molecules by systematic search of all orientations and evaluation of the resulting electrostatic interactions. TURNIP was applied to the transient interaction between two electron transfer metalloproteins, plastocyanin and cytochrome c. Our results suggest that the productive electron- transfer complex involves interaction of the positive region of cytochrome c with the negative patch of plastocyanin, consistent with experimental data. Application of TURNIP to the formation of the stable complex between the HyHEL-5 antibody and its protein antigen lysozyme showed that long-distance electrostatic forces guide lysozyme toward the HyHEL-5 binding site, but do not fine tune its orientation. Determination of docked antigen/antibody complexes requires including steric as well as electrostatic interactions, as we have done for the U10 mutant of the anti-phosphorylcholine antibody S107. We have enhanced the graphics program Flex, a convenient desktop workstation program for visualizing molecular dynamics and normal mode motions. Flex now has a user interface and has been rewritten to use standard graphics libraries, so as to run on most desktop workstations. Electrostatic recognition, Computer graphics, Protein binding, Electron transfer, Computational search.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1992
- Accession Number
- ADA264225
Entities
People
- Elizabeth D. Getzoff
- Victoria A. Roberts