John Brady is a Professor in the Department of Food Science at the Ithaca campus. He received a B.S. in Chemistry from the University of North Carolina at Chapel Hill in 1975, and a Ph.D. in Chemistry from the State University of New York at Stony Brook in 1980. During much of his graduate studies he was a visiting staff member at the Los Alamos National Laboratory in New Mexico. He received his postdoctoral training in Chemistry at Harvard University working with Prof. Martin Karplus. He joined the Cornell faculty in 1983.
Current Research
Molecular biophysics; molecular mechanics of carbohydrates; hydration of biological molecules; structure and function of proteins; structure/activity relationships in cellulases
Research Interests/Work in Progress
Our research primarily involves the dynamics and hydration of biopolymers, and of the relationship between structure, conformation, and function in biological systems. Specific examples includes the solution behavior of biopolymers, the factors which determine secondary and tertiary structure in polymers, enzymatic reaction mechanisms, rational drug design, the effects of point mutations in proteins, and the possibility of engineering desirable modifications in the function of wild-type proteins. In our work we use the techniques of computational theoretical chemistry to numerically model the properties of biopolymers and solutions. These techniques, often called Molecular Mechanics, include computer graphics-based molecular docking, energy minimization and conformational energy calculations, and molecular dynamics simulations.
A principal focus of our research is on the structure, dynamics, and hydration of carbohydrates, both because of their intrinsic importance and because they serve as useful models for the hydration of biological molecules in general. We have a broad effort underway to examine all aspects of carbohydrate structure and dynamics. Over the years we have contributed a number of advances in carbohydrate modeling, including the first molecular dynamics simulations on a sugar, the first relaxed conformational energy map for a disaccharide, the first free energy simulations of sugar energy differences in solution, and the first potential of mean force, or conformational free energy map, for a disaccharide. We have undertaken a series of studies to examine in detail the full three-dimensional structuring imposed on liquid water by carbohydrates in solution, and how this structuring depends upon the molecular architecture of the solute. We are particularly interested in developing simple geometric procedures for estimating the effects of hydration on specific molecular structures and combinations of functional groups. Projects are also under way to model the conformations and dynamics of various molecules of practical importance, including the carrageenans and cellulose, as a guide in understanding and manipulating the properties of these polymers.
We also have an active program in the study of protein structure, function, dynamics, hydration, and interactions with other molecules. Proteins of recent interest in our research have included b-lactoglobulin, xylose isomerase, the antifreeze polypeptide from winter flounder, and a variety of cellulases and lectins. Generally, but not always, the proteins which we model are selected due to their practical importance, either in industrial processes or in medical applications. Because of our primary interests in carbohydrates, we have a major effort under way to study the interactions of carbohydrates with proteins. As an example of a current project, we are using molecular mechanics simulations to study the catalytic mechanism and the mode of substrate binding in various cellulases, including the cellulase E2 from Thermomonospora fusca, in the hope of designing a more active enzyme which could be produced by site-directed mutagenesis.