Normal Mode Calculations of Icosahedral Viruses with Full Dihedral Flexibility by Use of Molecular Symmetry

The study of the dynamics and thermodn. of small icosahedral virus capsids is an active field of research.  Normal mode anal. is one of the computational tools that can provide important insights into the conformational changes of the virus assocd. with cell entry or caused by changing of the physicochem. environment.  Normal mode anal. of virus capsids has been limited due to the size of these systems, which often exceed 50,000 residues.  Here we present the first normal mode calcn. with full dihedral flexibility of several virus capsids, including poliovirus, rhinovirus, and cowpea chlorotic mottle virus.  The calcns. were made possible by applying group theor. methods, which greatly simplified the calcns. without any approxn. beyond the all-atom force field representations in general use for smaller protein systems.  Since a full Cartesian basis set was too large to be handled by the available computer memory, we used a basis set that includes all internal dihedral angles of the system with the exception of the peptide bonds, which were assumed rigid.  The fluctuations of the normal modes are shown to correlate well with crystallog. temp. factors.  The motions of the first several normal modes of each symmetry type are described.  A hinge bending motion in poliovirus was found that may be involved in the mechanism by which bound small mols. inhibit conformational changes of the capsid.  Fully flexible normal mode calcns. of virus capsids are expected to increase our understanding of virus dynamics and thermodn., and can be useful in the refinement of cryo-electron microscopy structures of viruses.