91
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.
