Biomolecular Interactions and Enzymatic Processes

Program Director/Principal Investigator (Last, First, Middle): Gao, Jiali Project Summary A multi-faceted research project is directed aimed at computational studies of photochemically induced processes and interactions in photoreceptor proteins. The theoretical approach centers on molecular dynamics and nonadiabatic quantum dynamics simulations of the ultrafast excited energy transfer and charge transfer as well as the subsequent protein conformation change that triggers signal transduction. We employ multiscale simulation techniques, including combined quantum mechanical and molecular mechanical (QM/MM) methods to describe intermolecular interactions. A major goal is to increase the capability of QM/MM methods to model photochemical processes and to achieve greater accuracy than conventional approaches. We propose to develop multistate density functional theory (MSDFT) to define excitation, charge, and spin localized states. We also plan on further explore the computationally efficient multistate tight-binding density functional theory (MS-DFTB) to perform long-time dynamics simulations. The MSDFT method follows a dynamic-then-static ansatz, in which dynamic correlation is incorporated into the basis states in the first place. As such, the basis configurations in the active space are highly contracted, which significantly reduce the number of configurations needed and the computational costs. Yet, MSDFT is also accurate. Applying the MSDFT/CHARMM combination, we aim to understand the nature of the photochemical and photophysical processes following light absorption in cryptochromes. In addition, we aim to understand the light harvesting mechanism of the ultraviolet-B receptor UVR8, and its light-induced dimer photodissociation process. A long- term goal is to understand the nature of protein-protein interactions between UVR8 and homologous proteins. PHS 398/2590 (Rev. 06/09) Page Continuation Format Page