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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM029553-07
Application #
3277219
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1984-06-01
Project End
1991-12-31
Budget Start
1990-07-01
Budget End
1991-12-31
Support Year
7
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Arts and Sciences
DUNS #
073134835
City
Medford
State
MA
Country
United States
Zip Code
02155
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