Mesoscale Model For The Self-Assembly And Cross-Linking Dynamics of HPV Virus-Like Particles

We present a novel Kinetic Monte Carlo modeling strategy to simulate the assembly and maturation of Human Papillomavirus (HPV) virus-like particles (VLPs) across a wide range of experimental conditions. The approach allows for the concurrent tracking of capsomeres during their assembly into HPV capsids and the formation of stabilizing intercapsomeric disulfide bonds (“L1 cross-linking”) in the real-time scale. The dynamical cross-linking process has been introduced in the model by using the mechanistic probability rules between involved L1 cysteine residues. The model incorporates real experimental data from an in vitro assembly system and the detailed information of VLP geometrical structure. We checked on the hypothesis related to important factors affecting the rates of capsid initiation, HPV VLP growth and cross-linking. The objective of this study was to leverage the model to advance the mechanistic understanding of the assembly and particle maturation process in order to screen for and prioritize process optimization strategies.