Thermodynamics and Kinetics of Protein Aggregation

点击翻译按钮获取中文摘要

The objective of this project is to investigate the problem of protein folding/unfolding, and in particular, the mediation of this process by the chaperone DnaK. This project involves both modeling and experimental studies. First, folding-aggregation competition will be studied. Measurements of interprotein interactions at varied external conditions, e.g. temperature, pH, and ionic strength, will help identify separate contributions to the overall interprotein potentials and their role in molecular association. The Principal Investigators (PIs) have developed a three dimensional periodic Monte Carlo simulator for capturing the competition between refolding and aggregation of initially unfolded protein-like chains. In this system various interactions on short length scales will be considered. Also, the PIs have predicted that the presence of pre-folded proteins improves the folding rate of unfolded proteins because of enhanced surface interactions. This provides a basis for modeling the chaperone-unfolded protein interaction so crucial in vivo. Other computational tasks include an understanding of the kinetics of the refolding process, since both folded and unfolded forms are thermodynamically feasible so that the kinetics may define the overall extent of folding.