RUI Protein Conformation: New Methods for Global Optimization and Parameter

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This project involves the development and improvement of a new conformational search strategy based on a convex global underestimator (CGU). The CGU search strategy has already been successfully tested on the Sun model for protein folding. This project will (1) speed up the CGU method for fast conformational searches and (2) improve the potential energy function by parameter estimation. Several enhancements will be used to speed up the method, including (a) using a core-directed chain growth method as a front end, (b) using the Han and Baker secondary structure rules, where applicable, to reduce the number of degrees of freedom, and (c) using Appel's method to reduce the number of required energy evaluations. To improve the search method so that it will work with better energy functions, this project will systematically move away from the Sun model toward more realistic protein potential functions and models. To do this, a new computational parameter estimation method that can simultaneously adjust all the energy function parameters will be developed, so as to reduce the difference between the global minimum conformation in the model and known native conformation for all members of a selected set of proteins.