title: Prediction of stability changes upon mutation in an icosahedral capsid.
abstract: Identifying the contributions to thermodynamic stability of capsids is of fundamental and practical importance. Here we use simulation to assess how mutations affect the stability of lumazine synthase from the hyperthermophile Aquifex aeolicus, a T = 1 icosahedral capsid; in the simulations the icosahedral symmetry of the capsid is preserved by simulating a single pentamer and imposing crystal symmetry, in effect simulating an infinite cubic lattice of icosahedral capsids. The stability is assessed by estimating the free energy of association using an empirical method previously proposed to identify biological units in crystal structures. We investigate the effect on capsid formation of seven mutations, for which it has been experimentally assessed whether they disrupt capsid formation or not. With one exception, our approach predicts the effect of the mutations on the capsid stability. The method allows the identification of interaction networks, which drive capsid assembly, and highlights the plasticity of the interfaces between subunits in the capsid.
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Hickman
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: James F
authors.initials: JF
authors.lastname: Ross
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
mesh_terms: D001419:Bacteria / Q000201:enzymology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D004795:Enzyme Stability; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D009097:Multienzyme Complexes; C044822:6,7-dimethyl-8-ribityllumazine synthase
keywords: capsids; free energy of association; lumazine synthase; modeling; protein engineering; self-assembly; simulation; stability