Devarajan Thirumalai is supported by a grant from the Theoretical and Computational to continue his research in statistical mechanical treatment of protein folding and protein dynamics. Work is proposed in four major areas: 1) the development of simple off lattice models representing the alpha carbons of proteins whose target native conformations are four helix bundles; 2) molecular dynamics studies of the effect of denaturants on the unfolding and refolding of proteins using minimal models; 3) extension of the minimal models to more realistic models that include the effects of side chains that can be used to model real proteins; and 4) use of instantaneous normal modes to characterize the rugged landscape of protein potential energy surfaces, and to further characterize the protein dynamics and optimal reaction pathways using these techniques. This theoretical approach will provide the basic understanding of the folding properties of protein. This problem is currently at the frontier of protein research, and a basic understanding of the factors that influence protein folding will have an enormous impact on the biotechnology industry.