Mesoscale model of the assembly and cross-linking of HPV virus-like particles

We present a novel kinetic Monte Carlo model to simulate the real process time-scale of the assembly of Human Papillomavirus (HPV) virus-like particles (VLPs) incorporating the formation of intercapsomeric disulfide bonds. The objective was to develop insights into the underlying mechanisms of HPV VLP assembly and cross-linking during in vitro production of the HPV vaccine. The model integrates actual experimental data and detailed information of VLP geometrical structure in microscopic mechanistic steps. The principal novelty of this model is in the concurrent simulation of VLP assembly and cross-linking including a variable for spatial angular arrangement of capsomeres during their assembly that affects the overall rates of VLP assembly and cross-linking. The cross-linking modeled by using the mechanistic probability rules between involved cysteine residues. The model was utilized to better understand the actual process data and check on the hypothesis related to factors affecting the rates of HPV growth and maturation.