Development and Application of Generalized Ensemble Algorithms for Protein-Folding

Michigan Technological University, Houghton MI

Investigators

Abstract

Ulrich Hansmann is cofunded with a grant from the Theoretical and Computational Chemistry and the Biophysics Program to develop of a generalized ensemble method for exploring the rugged energy landscapes found in proteins. New and improved algorithms will be developed for performing molecular simulations on proteins, and for the prediction of three dimensional structure for small peptides up to approximately 50 amino acids. The algorithms should prove useful in studies of thermodynamics of protein folding, and for investigating observed structural transitions. The PI has performed substantial testing of the new algorithms using Met-enkephalin as a benchmark, and will now extend the applications to larger systems including the chameleon peptide, Protein G, and a peptide fragment corresponding to the first 34 amino acids of human parathyroid hormone. A fundamental understanding of the way in which proteins fold is one of the grand challenges of current times. A theoretical understanding of this complex problem is made difficult by the high dimensionality and the ruggedness of the potential energy surface describing the protein conformational space. The challenge is to find a global minimum on this complex surface using currently available computer technology. Hansmann's research offers new ways of exploring this rugged landscape that will make the global minimum easier to locate.