Computational studies on rep and capsid proteins of CRESS DNA viruses

The circular rep-encoding single-stranded DNA viruses (CRESS DNA viruses) are among the smallest, with 2–6 kb ssDNA genomes that encode for a coat protein (C) and a replication protein (R). To comprehend the complexity and divergence of the C and R proteins, we have created predictive structural models of representative viruses infecting unique hosts from each family using the neural network-based method AlphaFold2 and carried out molecular dynamic simulations to assess their stability. The structural characteristics indicate that differences in loops and amino-terminus may play a significant role in facilitating adaptations to multiple hosts and vectors. In comparison to the C, the Rs show a high degree of conservation and structural mimicry of the nuclease-helicase domains of plasmids. A phylogenetic analysis based on the structures and sequences of the C and R proteins reveals evolutionary variances. Our study also highlights the conservation of structural components involved in the interaction of R with the conserved intergenic region of the genome. Further, we envisage that the adaptability of R's central linker may be crucial for establishing interactions with multiple protein partners, including C.