2026-10-10T15:53:26Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34060069 2026-10-02T22:04:21Z category_1 category_7 category_13 category_21 category_24 category_39 category_734 category_931 category_64 category_132 category_134 category_135 portal_63 item_type_3 month_year_10_2026

Topology-Aware Modeling of the Full Genome Reveals Stability Determinants in a Small Naked Virus Lucianna H. Silva Santos (25303714) Simón Poblete (3528539) Sergio Pantano (51689) Biophysics Medicine Genetics Biotechnology Evolutionary Biology Ecology Biological Sciences not elsewhere classified Information Systems not elsewhere classified Cancer Infectious Diseases Virology Computational Biology ∼ 20 nm yet differ substantially stranded dna genome standard reconstruction procedures simplified polymer representations resolution capsid structures predicted particle stability multiscale molecular dynamics extreme compaction observed energetically heterogeneous assemblies distinct genome arrangements dimensional topological models despite offering high circular ∼ 1 7 kb single obey icosahedral symmetry computational modeling offers 1 icosahedral capsid small dna viruses confined viral systems based structural prediction modeling genome topology icosahedral viruses aware modeling structural virology viral genomes thus averaged specific features simulate three results demonstrate ray crystallography produce virions pcv2 ), major obstacle internal energies generalizable framework fundamental challenge findings suggest environmental persistence electron microscopy complete virions complementary avenue circoviridae </ capture sequence Understanding how viral genomes are organized under extreme spatial confinement remains a fundamental challenge in structural virology. Icosahedral viruses, despite offering high-resolution capsid structures through cryo-electron microscopy and X-ray crystallography, present a major obstacle: their genomes do not obey icosahedral symmetry and are thus averaged out during standard reconstruction procedures, leaving genome topology largely unresolved. Computational modeling offers a complementary avenue, but existing approaches often rely on simplified polymer representations that fail to capture sequence-specific features and the extreme compaction observed in small DNA viruses. Here, we focus on Porcine Circovirus type 2 (PCV2), a member of the <i>Circoviridae</i> family and one of the smallest autonomous mammalian viruses, which packages a circular ∼1.7 kb single-stranded DNA genome into a ∼20 nm T = 1 icosahedral capsid at one of the highest DNA packing densities found in nature. We introduce an integrative methodology combining AI-based structural prediction, lattice Monte Carlo simulations, and multiscale molecular dynamics to generate and simulate three-dimensional topological models of the complete virions. Our results demonstrate that distinct genome arrangements can produce virions with experimentally indistinguishable external morphologies, yet differ substantially in their internal energies and predicted particle stability. These findings suggest that circovirus populations comprise structurally similar but energetically heterogeneous assemblies, with implications for infectivity, uncoating, and environmental persistence, while providing a generalizable framework for modeling genome topology in other confined viral systems. 2026-10-02T00:00:00Z Dataset Dataset 10.1021/acs.jcim.6c01934.s009 https://figshare.com/articles/dataset/Topology-Aware_Modeling_of_the_Full_Genome_Reveals_Stability_Determinants_in_a_Small_Naked_Virus/34060069 CC BY-NC 4.0