Kinetics of empty viral capsid assembly in a minimal model

Abstract

The efficient construction of a protective protein shell or capsid is one of the most crucial steps in the replication cycle of a virus. The formation of the simplest capsid typically proceeds by the spontaneous assembly of identical building blocks. This process can also be achieved in vitro even in the absence of genetic material, thus opening the door to the production of artificial viral cages for a myriad of applications. In this work, we analyze the efficiency and the kinetic peculiarities of this self-assembly process using Brownian Dynamics simulations. We use a minimal model that considers identical assembly units and is able to reproduce successfully the correct final architecture of spherical capsids. The selection of a specific size and structure is achieved by changing a single parameter that imposes an angular anisotropy on the interaction. We analyze how the geometrical constraints of the interaction affect the efficiency of the assembly. We find that the optimal conditions for an efficient assembly from a kinetic point of view strongly depart from the lowest capsid energy corresponding to the minimum of the potential energy landscape. Our work illustrates the important differences between the equilibrium and dynamic characteristics of viral self-assembly, and provides important insights on how to design specific interactions for a successful assembly of artificial viral cages.