IMPROVING BIOMOLECULAR SIMULATIONS: ENERGY FUNCTIONS AND CONFORMATIONAL SAMPLIN

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to continue our computational studies of the folding behavior of several model polypeptides with different secondary structure motifs and varying degrees of topological complexity. We seek insight into the nature of early events in protein folding and how folding and stability are related not only to specific interactions in the native structure but also to the composition of the unfolded ensemble. Small, fast-folding systems have become the subject of much recent research on protein folding, and our simulations will help provide detailed models for interpretation of experimental observations. Validation of methods and parameters via generation of hypotheses that are experimentally testable by our collaborators is a key aspect of our work. In addition, we propose to continue several other projects in DNA repair, tuberculosis drug discovery and protein force-field development.