Integrated Quantum, Moleucles, Solvatoin, Charge State Simulations of Proteins

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A protein's function and reactivity is the product of its atomic and electronic structure, its dynamics, and its cofactors. The goal of this research is to go beyond quantitative descriptions of how some reaction occurs to why it occurs, to an understanding of the events, at both the level of atoms or functional groups and in terms of principles. The nucleating theme of the program project is the concept of energy transduction or coupling, both as an overarching explanatory principle, and as an investigative tool. Novel measurements and analysis of internal and external Stark measurements on proteins (transduction of electrical energy into changes in spectral transition energies) will probe the environment of protein cofactors, and the mechanisms by which these proteins modulate cofactor function and reactivity. Analysis of high resolution spectroscopy will be used to study the relationship between solvent and protein dynamics and the protein's energy landscape (How the energy of solvent and protein fluctuations is transduced into other activated and functional modes), using recently integrated simulation and theoretical tools. The first aim of project # 4 is to develop a coherent suite of simulation technologies that can span the range from quantum chemical calculations of cofactor electronic structure, via simulation of protein motions, through to long time scale solvent, electrostatic and charge transfer effects, by combining quantum chemical calculations, classical dynamics and finite difference Poisson-Boltzmann methods. The second aim of project # 4 is to apply this suite of simulation technologies to specific problems: The effect of protein and solvent on heme properties, quantitative characterization of protein dynamics, and the effect of internal electrostatic fields of proteins.