Molecular shape dynamics, reaction paths and conformational transitions in biomolecules. Theory and simulations.

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Our research program focuses on developing and applying the tools of theoretical & computational chemistry to study the interplay between shape and dynamics in flexible molecules. Our approach blends the notions of structure, shape, energetics, and configurational transitions in an original manner: molecules are seen as topological entities, instead of isolated conformers at optimal geometries. By studying how these properties persist under external perturbations, we establish: (i) the stability of molecular shape, (ii) the factors that control the onset of configurational transitions, (iii) the occurrence of new species along reaction paths, and (iv) a measure of dynamic shape similarity for comparing these species. Molecular shape is conveyed differently depending on scale. For macromolecules, we use chain geometry and topology to monitor configurational transitions in constrained polymers and protein ions. In smaller systems, we focus on how quantum states and electronic structure are affected by external fields or non-adiabatic changes in nuclear geometry. Our long-term goal is to integrate these areas into a single protocol to study the interplay between local electronic properties and global conformational motions in biopolymers. The work projected for the next five years will extend our methods and apply them to the analysis of selected phenomena. The following main themes will be our priorities: (a) Configurational transitions in grafted and externally-driven polymers with distinct topologies. (b) The stability and unfolding of anhydrous protein ions in conditions that simulate time-of-flight mass spectrometry. (c) Effect of external fields and nuclear geometry on the curvature for reaction paths for electronic processes. The themes (a) and (b) rely on a combination of polymer theory, computer simulations, and our techniques to study chain entanglement. Theme (c) deals with non-adiabatic effects caused by the motions and local fields associated with a protein native state. This latter analysis requires the computation of diabatic amplitudes in coherent quantum states that vary with external fields. I will continue to train HQPs in these areas, and pursue collaborative research with colleagues in Sweden during my sabbatical in 2010/2011.