All-atom normal-mode analysis reveals an RNA-induced allostery in a bacteriophage coat protein.

Assembly of the T=3 bacteriophage MS2 is initiated by the binding of a 19 nucleotide RNA stem loop from within the phage genome to a symmetric coat protein dimer. This binding event effects a folding of the FG loop in one of the protein subunits of the dimer and results in the formation of an asymmetric dimer. Since both the symmetric and asymmetric forms of the dimer are needed for the assembly of the protein container, this allosteric switch plays an important role in the life cycle of the phage. We provide here details of an all-atom normal-mode analysis of this allosteric effect. The results suggest that asymmetric contacts between the A -duplex RNA phosphodiester backbone of the stem loop with the EF loop in one coat protein subunit results in an increased dynamic behavior of its FG loop. The four lowest-frequency modes, which encompass motions predominantly on the FG loops, account for over 90% of the increased dynamic behavior due to a localization of the vibrational pattern on a single FG loop. Finally, we show that an analysis of the allosteric effect using an elastic network model fails to predict this localization effect, highlighting the importance of using an all-atom full force field method for this problem.