Multiscale Theory and Simulation of Chemical Systems

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Many important questions in science involve phenomena acting upon varying length and time scales. For example, in biology, the binding of a ligand to a protein (atomistic event) can trigger changes in secondary and tertiary structure which then affect protein complex formation (mesoscopic event) which then affects biological activity in a cell (macroscopic event). This proposal seeks to utilize and develop multiscale modelling methods which can be used to answer questions involving disparate scales. This is broken down into three main themes. 1. Using coarse-grained or all-atom molecular dynamics techniques coupled with charge migration algorithms, the dissociation of gas phase protein complex ions will be studied.  Proof of concept simulations will explore the use of basic-site containing tethers to sequester charge in a complex, and create repulsive forces tailored at predefined positions, with the goal of producing site-directed dissociation forces.  The ability to dissociate a protein complex in a predefined manner will broaden immensely the experimental tools available for analyzing protein complex structure by mass spectrometry.  These methods require only commonly used chemical modifications of proteins.  With such methods, mass spectrometrists will be able to unlock the interactions in protein complexes and translate this back into biological function in cells. 2. The effect of nanoparticles on lipid vesicles will be investigated using a hybrid simulation methodology that treats some parts of a system atomistically, and other parts with a coarse-grained force field.  The hybrid method treats the two regions in a physically consistent way, while at the same time allowing detailed structural and even chemical effects to be described in areas of importance (the atomistic region).  There is intense interest in this problem due to health concerns over nanoparticle toxicity. 3. A method for correcting dynamical timescales in coarse-grained simulations will be explored in two ways.  First, by considering a system described completely with dissipative particle dynamics in which the necessary fluctuating forces are determined from atomistic molecular dynamics.  Second, by considering a hybrid method coupling an atomistic region treated with molecular dynamics with a mesoscopic region treated with dissipation particle dynamics.  In both cases, the result will be a coarse-grained description of the system fed by atomistic information for self-consistency.  A coarse-grained method with accurate dynamics can revolutionize simulation applications in a wide variety of fields, including materials science, biology, chemistry, and physics.