{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/rapid-prediction-of-crucial-hotspot","title":"Rapid prediction of crucial hotspot interactions for icosahedral viral capsid self-assembly by energy landscape atlasing validated by mutagenesis","arxiv_id":"2001.00316","date":"2020-01-02","proceeding":null,"authors":["Ruijin Wu","Rahul Prabhu","Aysegul Ozkan","Meera Sitharam"],"abstract":"Icosahedral viruses have their infectious genome encapsulated by a shell assembled by a multiscale process, starting from an integer multiple of 60 viral capsid or coat protein (VP) monomers. We predict and validate inter-atomic hotspot interactions between VP monomers that are important for the assembly of 3 icosahedral viral capsids: Adeno Associated Virus serotype 2 (AAV2) and Minute Virus of Mice (MVM), both T=1 single stranded DNA viruses, and Bromo Mosaic Virus (BMV), a T=3 single stranded RNA virus. Experimental validation is by in-vitro, site-directed mutagenesis data found in literature. We combine ab-initio predictions at two scales: at the interface-scale, we predict the importance (cruciality) of an interaction for successful subassembly across each interface between VP monomers; and at the capsid-scale, we predict the cruciality of an interface for successful capsid assembly. At the interface-scale, we measure cruciality by changes in the capsid free-energy landscape partition function when an interaction is removed. The partition function computation uses atlases of interface subassembly landscapes, rapidly generated by a novel geometric method and curated opensource software EASAL (efficient atlasing and search of assembly landscapes). At the capsid-scale, cruciality of an interface for successful assembly of the capsid is based on combinatorial entropy. Our study goes from resource-light, multiscale computational predictions of crucial hotspot inter-atomic interactions to validation using data on site-directed mutagenesis' effect on capsid assembly. By reliably and rapidly narrowing down target interactions, (no more than 1.5 hours per interface on a laptop with Intel Core i5-2500K 3.2Ghz CPU and 8GB of RAM) our predictions can inform and reduce time-consuming in-vitro and in-vivo experiments, or more computationally intensive in-silico analyses.","url_abs":"https://arxiv.org/abs/2001.00316v4","url_pdf":"https://arxiv.org/pdf/2001.00316v4.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[{"paper_slug":"rapid-prediction-of-crucial-hotspot","repo_url":"https://bitbucket.org/geoplexity/easal","is_official":1,"mentioned_in_paper":1,"mentioned_in_github":0,"framework":"none","reach":null}],"tasks":[{"task_slug":null,"task_name":"CPU"}],"methods":[],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"syntology_url":null,"atlas_url":null,"mcp":null,"developers":"https://syntology.ai/developers"},"arxiv_metadata":null,"syntology_extracted_results":null}