Computational approaches to modeling viral structure and assembly

The structures of biological macromolecules and macromolecular assemblies can be experimentally determined by X-ray crystallography, nuclear magnetic resonance (NMR), and cryo-electron microscopy (cryo-EM). The refinement of such structures is a difficult task, because of the size of the experimental data sets, and because of the very large number of degrees of freedom. Molecular modeling tools-particularly those based on the principles of molecular mechanics-have long been employed to assist in the refinement of macromolecular structures. Molecular mechanics methods are also used to generate de novo models when there are only limited experimental data available. Ideally, such models provide information on structure-function relationships, and on the thermodynamic and kinetic properties of the system of interest. Here, we summarize some of the molecular mechanics methods used to investigate questions of viral structure and assembly, including both all-atom and coarse-grained approaches.