Abstract
Assembly of even a simple virus is a complex reaction. Yet, in many cases, the capsids of isometric viruses assemble spontaneously and with high fidelity in vitro. In vitro reactions can be used as the basis for interpreting assembly in vivo, searching for assembly-directed small molecules, or subverting normal assembly to generate novel structures. A model is required to interpret experimental observation of any complex reaction. To this end, we developed a thermodynamickinetic (master equation) model, in which assembly is described in terms of a cascade of low order reactions. The resulting model can readily be adjusted to match the specific features of a biological system. Simulations replicate experimental observations of assembly and lead to experimentally testable predictions. Analyses based on a basic model, in which only a single path from monomer to capsid was posited, are equally applicable to sparse and complete models that include selected intermediates and every possible intermediate, respectively.