This project, jointly supported by Molecular Biophysics in the Division of Molecular and Cellular Biosciences and the Theoretical and Computational Program in the Chemistry Division, will use novel computer simulation techniques to study the mechanism of folding of proteins. The main computational algorithm to be employed is the stochastic difference equation in length (SDEL), a boundary value method that permits the calculation of trajectories connecting two known (boundary) states of the system. This methodology allows viewing, with atomic detail, long time dynamical processes that were impossible to study before by computer simulations. The folding process of globular single-domain proteins (apomyoglobin and bovine beta-lactoglobulin) and multi-domain proteins (gene-3 protein of phage fd and the phosphoglycerate kinase) will be considered in aqueous environment by simulating explicitly the water molecules. Most of these systems have not been studied before by computer simulations because of their large size and their slow folding times. Also, an implicit water/membrane model based on a continuum dielectric treatment (the Generalized Born theory) will be used to study the insertion and folding of membrane-bound peptides and proteins with unprecedented detail. The embedding and folding of simple peptides like mellitin and the dimeric transmembrane domain from glycophorin A will be considered first. Later on, folding simulations of more complex and biologically relevant proteins like the K+ channel KscA, the monomeric beta-barrel OmpA porin and Bacteriorhodopsin will be studied.
This project will promote the training of graduate and undergraduate students. The research and methodologies will be used as thematic material in the Research Experience for Teachers program at the University of South Florida in which school teachers design lesson plans for their classrooms based on research performed during the summer. The Research Experience for Teachers program has the potential to instill in many middle and high school students the love for science through the lessons designed by their teachers. Also, the success of Hispanic school students in the Tampa area and their enrollment to college will be supported through participation in a special social program at the University of South Florida.
