Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

45-POS Board 45 Modeling Multi-Protein Assembly Processes Using Single-Particle Reaction Diffusion Margaret Johnson . Johns Hopkins University, Baltimore, MD, USA. Biological processes ranging from receptor mediated signaling to clathrin-mediated endocytosis depend on populations of distinct proteins competing and cooperating to stochastically form protein complexes at the membrane and in solution. The recruitment of proteins to both the membrane surface and to growing protein complexes can significantly alter a protein’s dynamics and subsequent binding reactions. Building accurate models of these complex processes therefore requires tracking both the spatial and temporal evolution of proteins and their higher order assemblies. The challenge for these models lies in accurately reproducing experimentally known reaction rates between protein domains while correctly accounting for multi-protein complex formation at time scales of seconds or longer. We show how a recently developed algorithm for efficient simulation of single-particle protein-protein interactions can be extended to model protein recruitment and binding on the membrane, as well as specific protein-domain interactions. This free-propagator reweighting (FPR) method combines simple position updates to the proteins using free diffusion along with a trajectory reweighting method that allows us to recover the correct association rates for all binding interactions. The method extends readily from 3D solution to the 2D membrane, and the approach can correctly reproduce effects of rotational motion and orientational contraints on protein-protein interactions. With this level of spatial and structural resolution we are uniquely able to quantify the changes in protein binding dynamics that occur upon membrane binding and complex formation. With an assembly process such as occurs in the early stages of clathrin-mediated endocytosis, changes in the interaction dynamics could provide important controls for the successful formation of the clathrin protein coat, where protein motion is constrained by other proteins and by the membrane.

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