Speakers
Dr
Christoph Globisch
(Max-Planck-Institut für Polymerforschung, Mainz)Dr
Venkatramanan Krishnamani
(Carnegie Mellon University, Pittsburgh)
Description
The major protective coat of most viruses is a highly
symmetric protein capsid that forms spontaneously from many
copies of identical proteins. Structural and mechanical
properties of several such capsids, as well as their
self-assembly process, have been studied experimentally and
theoretically, including modeling efforts by computer
simulations on various scales. Atomistic models include
specific details of local protein binding but are limited to
small time- and length-scales, while coarse grained (CG)
models capture the scales to study protein assembly but
often lack the specific local interactions. Multiscale
models aim at bridging this gap by systematically connecting
different levels of resolution. We have started to develop a
multiscale simulation approach to study the protein capsid
complex of the Cowpea Chlorotic Mottle Virus (CCMV), a plant
virus with an icosahedral symmetric (T=3) shell of 180
identical proteins. Here, we link simulations at different
levels of resolution by parameterizing CG models using
atomistic simulations of monomers. From this CG level, we
predict emergent properties of larger aggregates, which are
possible intermediates in the assembly process or otherwise
relevant for the mechanical stability of the virus shell.
Atomistic (united atom) molecular dynamics simulations in
aqueous solution were carried out to study the conformations
sampled by these aggregates (on the limited timescale that
is accessible to these simulations) and to investigate the
interactions at the protein interface. On the CG side we
have used and refined two types of models, the MARTINI model
(3-4 heavy atoms per CG bead, explicit water representation)
[1] and a recently developed implicit solvent protein model
by Bereau and Deserno [2].
[1] Marrink, S. J., Risselada, H. J., Yefimov, S., Tieleman,
D. P., and de Vries, A. H. (2007) The MARTINI force field:
coarse grained model for biomolecular simulations, J Phys
Chem B 111, 7812-7824.
[2] Bereau, T., and Deserno, M. (2009) Generic
coarse-grained model for protein folding and aggregation, J
Chem Phys 130, 235106.
