Molecular modeling of the PCV2d virus-like particle from coarse-grained molecular dynamics simulations

FRIGINI, EZEQUIEL N.; PANTANO, SERGIO

Rosario, Santa Fe

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Porcine circovirus (PCV2) is a member of the genus Circovirus. PVC is a small, naked, icosahedral virus (≈ 19 nm diameter) possessing a circular single-stranded DNA genome. Currently, four strains of PCV have been identified: PCV1, PCV2, PCV3, and PCV4. In particular, the PCV2 strain is pathogenic for pigs, causing significant economic losses in pig production in Argentina and the world. The viral capsid structures of only a few PCV2 genotypes are known. In this work, we carried out coarse-grained molecular dynamics using the structure of the PCV2d genotype (PDB code:6OLA), which is the predominant genotype worldwide. Coarse-grained simulations using SIRAH 2.0 force field were used to elucidate the mechanism of destabilization and opening of the capsid of the PCV2d. For this purpose, we performed coarse-grained molecular dynamics simulations of the whole virus at different temperatures, from room temperature to 370 K. A high correlation between the dynamic conformational ensemble and CryoEM data highlighted the capacity of the simulations to reproduce the experimental data. Analysis of structural and dynamical descriptors allowed us to pinpoint critical regions for the stability of the viral particle, which are associated with the icosahedral symmetry axes. In particular, we identified an increased distortion around the 5-fold symmetry axis with a significant loss of native contact. These distortions become more pronounced at 340 K, suggesting a melting point near that temperature.Moreover, we found a marked correlation between highly flexible regions with poorly conserved amino acids in this viral genotype. These findings suggest possible mutable sites that will allow engineering viral particles without compromising their stability to develop novel vaccine prototypes.