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. Proteins 2015; 83:1733–1741. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc

Decorating Self-Assembled Peptide Cages with Proteins

“…In addition to these protein-engineering approaches, others are exploring rational design and assembly of addressable, nanoscale, biologically inspired containers. − This includes containers constructed from virus-like particles, , DNA origami, − vesicles, natural , and de novo protein assemblies, − and peptide shells. − More specifically, several groups have constructed protein-based supramolecular assemblies by exploiting the symmetry of natural multimeric proteins. This is achieved by fusing together two naturally occurring protein domains with different oligomerization properties, e .…”