The University of California at Merced has been awarded a grant to develop new tools and protocols for characterizing protein dynamics. While the focus of protein biophysics has traditionally been on the structure and interactions of the natively folded protein, there is now rapidly growing interest in the properties of denatured protein structures as related to the mechanisms of protein folding and in the function of so-called intrinsically disordered proteins. Molecular simulations have great promise in helping to understand disordered proteins; however, new tools are needed to characterize the defining property of these constantly changing systems--their dynamics. The long-term goal of this research is to develop new tools and protocols for determining the two most fundamental descriptors of protein dynamics, the effective dimensionality of the motion and the volume of structural space sampled by the protein. The tools will help answer the many fundamental, unresolved questions about the denatured or disordered states of proteins that are central to understanding protein function and folding. Specifically, these tools will determine to what extent denatured or intrinsically disordered proteins behave as random polymers or have motions constrained to lower dimensional dynamics. Additionally these tools will elucidate whether there are differences between the dynamics of intrinsically disordered proteins and natively folded proteins in the early stages of folding. Finally, these tools will help in determining the efficiency of different molecular simulations in sampling the denatured or disordered states of proteins.
This project will be an ideal multidisciplinary training experience for the students involved since it brings together three scientific disciplines: machine learning, molecular simulation, and polymer biophysics. The tools developed in this project will be used by graduate and undergraduate students in both molecular simulation and computer sciences courses at UC Merced and by students in summer research projects. The molecular dynamics community has a well established tradition of software tools that are developed and maintained by individual research groups and freely distributed to very large user bases. These established channels will be used to freely distribute all of the software tools developed in this project in source code format along with documentation and test data sets. More information can be found at the project website: http://vision.ucmerced.edu/projects/protein.
