Computer Simulation Studies of the Thermodynamics and Kinetics of Protein Folding and Aggregation

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ABSTRACT CTS-9704044 Carol Hall/N.C. State This proposal describes a program of theoretical research aimed at understanding the mechanisms by which solutes such as polyethylene glycol (PEG) enhance the refolding of proteins and prevent aggregation. The goal is to develop molecular-level models that capture the essential features that govern the competition protein refolding and aggregation in both the presence and absence of solutes. By simulating the properties of model proteins and solutes on the computer, we will be able to explore how protein folding and kinetics are influenced by: protein type and concentration; denaturant type and concentration; solute type; concentration, and size; and temperature. The investigators will work on three parallel tracks whose objectives are: (1) to extend the two dimensional lattice Monte Carlo studies of protein folding and aggregation previously performed under NSF sponsorship to include the presence of model solutes that mimic the effect of PEG, (2) to develop simple off-lattice models based on the heteronuclear square-well chain model and then to use discontinuous molecular dynamic (DMD) to simulate protein folding and aggregation in the presence and absence of model PEG molecules. ***