Theoretical Studies of Membrane Proteins

9808902 Honig This project represents the continuation of a research program whose overall objective is to further understanding of the physical principles that determine the structure and function of membrane proteins. Theoretical calculations based primarily on numerical solutions to the Poisson-Boltzmann equation will be used to study important biological processes such as the association of proteins with membrane surfaces, lateral domain formation in lipid bilayers and protein-protein interactions in src family kinases. Electrostatic free energies obtained from the calculations will be used construct testable models which can explain that remarkable localization phenomena that lead to the formation of distinct phases in biological membranes and to the precise recognition of specific protein domains for one another. Subcellular localization is a central feature of many biological phenomena such as viral assembly and signal transduction. At present there is only limited understanding of the processes that underlie these phenomena and their physical-chemical basis is even more poorly understood. The proposed calculations and the related collaborations with experimental groups are intended to fill this existing gap in knowledge by providing detailed atom-level explanations of localization and specificity near membrane surfaces.