THEORETICAL INVESTIGATIONS OF DNA POLYMERASES

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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. In the realm of fundamental and applied sciences, the interface between nanotechnology and biotechnology is rapidly evolving. At this interface, quantitative description of underlying fundamental processes is inherently a multiscale problem. In this proposal, we strive to achieve a multiscale description of equilibrium and dynamic processes associated biomolecular interactions by pursuing the following aims. (1) Develop and apply free energy methods in conjunction with a quantum mechanics molecular mechanics (QMMM) Hamiltonian to describe enzyme catalytic mechanisms. (2) Apply free energy methods in conjunction with molecular dynamics to descrive enzyme conformational activation and substrate recognition. (3) Develop and apply multiscale spatially resolved hybrid deterministic/ stochastic algorithms for studying signal transduction. The proposed studies are likely to have a significant impact in nanobiotechnology and systems biology in terms of enabling fundamental scientific discoveries, as well as driving rational design.