Professor; DPhil, Oxford University, England; Postdoctoral Fellow, Princeton University and California Institute of Technology; Rhodes Scholar; Alfred P. Sloan Fellow; UCLA Distinguished Teaching Award; John Simon Guggenheim Fellow; UCLA Faculty Research Lectureship; National Academy of Sciences Member; American Academy of Arts and Sciences Member.

Description of Research:

In our group, protein structures are determined by x-ray crystallography, and structures are related to function by biochemical and genetic methods. At present the structure and action of half a dozen proteins are being studied. These include the multisubunit, regulated enzymes glutamine synthetase and RuBisCO; diphtheria toxin, a proenzyme that crosses the cell plasma membrane and stops protein synthesis; and several designed proteins. Excellent facilities for structure determination are shared with other members of the Biological Structure Group.

A central question of biochemistry is how the amino acid sequence of a protein determines its three-dimensional structure. The goal is to be able to predict the structure from the sequence, a matter of great practical importance. One computational approach being developed is to describe a 3D structure by a 3D profile. The 3D profile can score the compatibility of any amino acid sequence with the 3D structure. A high compatibility score indicates the sequence may be folded as the structure. A second approach is to test rules of protein folding by designing and synthesizing a simple protein, and then using x-ray crystallography to compare the actual structure with the design.

What are the interactions that stabilize proteins or which permits proteins to recognize other proteins or small molecules? These questions are being explored with hydrophobic moments and Atomic Solvation Parameters (ASPs). These are semi-empirical quantities that characterize interactions of amino acid residues. ASPs give an estimate of the hydrophobic contribution to the free energy of interaction.

Eisenberg Research Group

Key words:

Molecular Biology and Physical Chemistry: protein structure; protein folding and design profiles; protein stability and biological recognition.

Last Revision: 10/26/95 // mk