The purpose of this research is to contribute the understanding of protein folding by carrying out theoretical studies that develop methods for predicting the folded conformations of a protein in a given environment and the characteristics of transitions among the conformations. This is essential for a rational approach to protein engineering or the design of drugs that bind protein receptors, since there are too many natural and artificially producible polypeptides to determine their structures by physical methods alone. The research is divided into three parts: I. Applications of the Diffusion-Collision Model of Protein Folding including a comparative study of the folding kinetics, intermediate states and folding pathways of the globin family and an extension of the methodology to beta-sheet proteins with an application to prealbumin. II. Simulation Studies of Secondary Structure Interactions using Brownian dynamics methods applied to polypeptide chains with three alpha-helices, beta-strand beta-strand interactions and properties of beta-alpha-beta polypeptide chains. III. Protein Structure Prediction by a Combined Dynamical and Static Approach applied to the globins, the gamma-crystallins, the aspartic proteinases renin and the beta-crystallins which have undetermined crystal structures.
| Fezoui, Y; Weaver, D L; Osterhout, J J (1994) De novo design and structural characterization of an alpha-helical hairpin peptide: a model system for the study of protein folding intermediates. Proc Natl Acad Sci U S A 91:3675-9 |
| Yapa, K; Weaver, D L; Karplus, M (1992) Beta-sheet coil transitions in a simple polypeptide model. Proteins 12:237-65 |
