  In this article we use all-atom simulations to elucidate the mechanisms
underlying conformational switching and allostery within the coat protein of
the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that
the capsid protein adopt different conformations at precise locations within
the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2
genome acts as an allosteric effector, guiding conformational switching of the
coat protein during capsid assembly. Since the principal conformational changes
occur far from the TR binding site, it is important to understand the molecular
mechanism underlying this allosteric communication. To this end, we use
all-atom simulations with explicit water combined with a path sampling
technique to sample the MS2 coat protein conformational transition, in the
presence and absence of TR-binding. The calculations find that TR binding
strongly alters the transition free energy profile, leading to a switch in the
favored conformation. We discuss changes in molecular interactions responsible
for this shift. We then identify networks of amino acids with correlated
motions to reveal the mechanism by which effects of TR binding span the
protein. The analysis predicts amino acids whose substitution by mutagenesis
could alter populations of the conformational substates or their transition
rates.
