TCBG Seminar

“Macromolecular Assemblies Understood via Coupled Evolution of Coarse-Grained and Atomistic Variables”

Dr. Abhishek Singharoy
Department of Chemistry
Indiana University
Bloomington, Indiana

Friday, June 1, 2012
3:00 pm (CT)
3269 Beckman Institute


Physicochemical processes underlying the organization of macromolecular assemblies are often characterized by a hierarchy of spatio-temporal scales. The unified theme of my research is to delineate ways in which the laws of physics and chemistry operate across these scales to yield biologically relevant structure and function. In this context, first, an assembly is described via a reduced model cast in terms of a set of space warping collective variables. These variables capture coherent, low-frequency deformations of the assembly; while our mathematical reformulation of the underlying molecular physics simultaneously accounts for high frequency atomic fluctuations. With this, macromolecular assembly behavior is understood via the slow Langevin-type dynamics of coarse-grained variables coupled with the quasi-equilibrium probability density for rapidly fluctuating atomic configurations. Computational implementation of this algorithm results in efficient all-atom simulations of assembly dynamics. The methodology is further extended to facilitate a variety of data-guided simulations for identifying multiple free energy minimizing states of a system. Following a similar strategy, spatial separation between fine-scale and coarse-grained features of nanoscale assemblies is employed to formulate a Poisson Boltzmann approach for investigating their electrostatic properties. The above suit of multiscale techniques is applied to investigate structural transitions in a range of biological systems including iron binding protein lactoferrin, T=1(Satellite Tobacco Mosaic Virus, Human Papilloma Virus), T=3 (Cowpea Chlorotic Mottle Virus) and T=7 (Simian) viruses. Simulation results imply a set of molecular scale metrics that correlate virus structure and fluctuations to their possible immunogenicity. These concepts are guiding the design of novel silica nanoparticle based vaccines against cervical cancer.

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