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

38-POS Board 38 CCMV Capsid Deformation Studied by Multi-Scale Simulation Techniques - Link towards Understanding of the Aggregation Process Christoph Globisch 1,2 , Venkatraman Krishnamani 3,4 , Markus Deserno 3 , Christine Peter 1,2 . 1 University of Konstanz, Konstanz, Germany, 2 Max Planck Institute for Polymer Research, Mainz, Germany, 3 Carnegie Mellon University, Pittsburgh, PA, USA, 4 University of Iowa, Iowa City, IA, USA. Here we report on our coarse graining efforts of CCMV (Cowpea Chlorotic Mottle Virus), an icosahedrally symmetric plant virus consisting of 180 identical protein monomers. We utilize atomistic simulations of dimers for construction and optimization of a supportive elastic network used with a MARTINI-level CG model. This approach allows us to predict inter- protein conformational flexibility and properties of larger capsid fragments and reproduces experimental (Atomic Force Microscopy) indentation measurements of the entire viral capsid. Later on we extend the AFM mimicking simulations to look into the breaking process of the virus until its ultimate structural failure and develop an automated method to analyze these huge trajectories. The method approaches the virus at different resolution levels and allows for classification of the capsomer interfaces in terms of symmetry classes and structure deformation at the protein level but can also track down to the residue level. The symmetry-classes differ substantially in their stability and appear to backtrack the putative assembly pathway: the reverse stability order resembles the believed sequence. Dimers and pentamers of dimers (first and second assembly step) never fail while hexamers of dimers (last assembly step) do. While the wild type capsid fortifies this location with a cooperatively formed 6-stranded beta-barrel motif, the mutant we employed in our studies misses this part. Therefore we hypothesize that the assembly order is regulated by the strengths of the interfacial binding, but the late and weak spots may be reinforced by cooperative motifs that form post-assembly.

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