1 research outputs found
Predicting the Initial Steps of Salt-Stable Cowpea Chlorotic Mottle Virus Capsid Assembly with Atomistic Force Fields
Computational prediction of native protein–protein interfaces
still remains a challenging task. In virus capsids, each protein unit
is in contact with copies of itself through several interfaces. The
relative strengths of the different contacts affect the dynamics of
the assembly, especially if the process is hierarchical. We investigate
the dimerization of the salt-stable cowpea chlorotic mottle virus
(CCMV) capsid protein using a combination of different computational
tools. The best predictions of dimer configurations provided by blind
docking with ZDOCK are rescored using geometry optimization with the
Amber and Rosetta force fields. We also evaluate the relative stabilities
of the three main interfaces present in the icosahedral capsid using
locally restricted docking with Rosetta. Both the rescoring and locally
restricted docking results report a particularly stable protein–protein
interface, which is the most likely intermediate during the first
stage of the hierarchical capsid assembly. The blind docking results
rescored with both Amber and Rosetta yield docking funnels, i.e.,
three or more near-native structures among the top five predictions.
The results support experimental observations on in vitro assembly
of CCMV capsids. The cross-validation of the results suggests that
energy-landscape-based methods with biomolecular force fields have
the potential to improve existing docking procedures