Biologic Constraints on Modelling Virus Assembly英文文献资料.docVIP

ComputationalandMathematicalMethodsinMedicine Vol.9,Nos.3–4,September–December2008,257–264 Biologicconstraintsonmodellingvirusassembly RobertL.Garcea* DepartmentofPediatricHematology/Oncology,UniversityofColoradoSchoolofMedicine, Aurora,CO,USA (Received20January2008;?nalversionreceived29April2008) The mathematic modelling of icosahedral virus assembly has drawn increasing interest because of the symmetric geometry of the outer shell structures. Many models involve equilibriumexpressionsofsubunitbinding,withreversiblesubunitadditionsformingvarious intermediatestructures.Theunderlyingassumptionisthata?nallowestenergystatedrives theequilibriumtowardassembly.Intheirsimplestforms,thesemodelshaveexplainedwhy high subunit protein concentrations and strong subunit association constants can result in kinetictrapsformingoffpathwaypartialandaberrantstructures.However,thecellbiologyof virus assembly is exceedingly complex. The biochemistry and biology of polyoma and papillomavirusassemblydescribedhereillustratesmanyofthesespeci?cissues.Variables includetheuseofcellular‘chaperone’proteinsasmediatorsofassembly?delity,thecoupling ofassemblytoencapsidationofaspeci?cnucleicacidgenome,theuseofcellularstructures as ‘workbenches’ upon which assembly occurs, and the underlying problem of making a capsidstructurethatismetastableandcapableofrapiddisassemblyuponinfection.Although formidable to model, incorporating these considerations could advance the relevance of mathematicalmodelsofvirusassemblytotherealworld. Keywords:polyomavirus;papillomavirus;virusassembly;chaperoneproteins Themathematicmodellingofvirusassemblyhasdrawnincreasinginterestoverthepastdecade. In particular, icosahedral viruses have been attractive targets because of their symmetric geometry.Assemblymodelshaverangedfrom‘coarse’ to‘?ne grain’approximations,using geometric shapes interacting by a ?xed set of predetermined rules, to molecular dynamic calculations predicting the lowest energy state of interacting protein