Project Summary Our long-term objective is to ascertain how protein conformation plays a role in biological function and in various diseases. Our specific aims are to combine a new physics-based method for homology searching, the Property Factor Method (PFM), with our coarse- grained UNRES potential energy function, and with all-atom potentials, to model several biological systems related to specific diseases. We will also continue the development of the PFM approach, with a view to improving the success of homology modeling. We will demonstrate how these aims can lead to valid predictions of structures and folding pathways of proteins. Our main focus will involve the application of this methodology to specific biological problems.