Theoretical analysis and computer simulations will be used to address a number of problems associated with membrane proteins. The goals will be to develop insights, computational methodologies and models which will facilitate the design and interpretation of experiments on membrane proteins in general and retinal proteins in particular. Dr. Honig will focus on three general areas: 1) he will address electrostatic questions with a recently developed method to obtain electrostatic energies of macromolecular systems; 2) he will develope methods to predict amino-acid side-chain conformations and helix-helix orientations in membrane proteins; and 3) he will continue efforts to understand the structure and function of retinal proteins. In the past few years there has been a large increase in the understanding of the structure of membrane proteins. A significant number of amino acid sequences have been reported and these have revealed remarkable homologies between different families of proteins. Sequence analysis and some structural information has suggested that many transmembrane proteins share common structural elements. In particular, it appears that alpha helices are a major structural motif in membrane proteins. A number of laboratories now have the capability of modifying proteins essentially at will. The problem though is what to modify. There is an absence of well-defined testable models, due in part to uncertainties as to the principles that govern the structure and function of membrane proteins. This project, hopefully, should help to overcome this.
