arXiv subjects

Michael F Hagan

Publications and source records attributed to Michael F Hagan.

3 recordsLinked to original sources

arXiv2014

Mechanisms of virus assembly

Viruses are nanoscale entities containing a nucleic acid genome encased in a protein shell called a capsid, and in some cases surrounded by a lipid bilayer membrane. This review summarizes the physics that govern the processes by which capsids assembles within their host cells and in vitro. We describe the thermodynamics and kinetics for assembly of protein subunits into icosahedral capsid shells, and how these are modified in cases where the capsid assembles around a nucleic acid or on a lipid bilayer. We present experimental and theoretical techniques that have been used to characterize capsid assembly, and we highlight aspects of virus assembly which are likely to receive significant attention in the near future.

q-bio.BM↗

arXiv2014

Pathways for virus assembly around nucleic acids

Understanding the pathways by which viral capsid proteins assemble around their genomes could identify key intermediates as potential drug targets. In this work we use computer simulations to characterize assembly over a wide range of capsid protein-protein interaction strengths and solution ionic strengths. We find that assembly pathways can be categorized into two classes, in which intermediates are either predominantly ordered or disordered. Our results suggest that estimating the protein-protein and the protein-genome binding affinities may be sufficient to predict which pathway occurs. Furthermore, the calculated phase diagrams suggest that knowledge of the dominant assembly pathway and its relationship to control parameters could identify optimal strategies to thwart or redirect assembly to block infection. Finally, analysis of simulation trajectories suggests that the two classes of assembly pathways can be distinguished in single molecule fluorescence correlation spectroscopy or bulk time resolved small angle x-ray scattering experiments.

q-bio.BM↗

arXiv2011

Prolonging assembly through dissociation:A self assembly paradigm in microtubules

We study a one-dimensional model of microtubule assembly/disassembly in which GTP bound to tubulins within the microtubule undergoes stochastic hydrolysis. In contrast to models that only consider a cap of GTP-bound tubulin, stochastic hydrolysis allows GTP-bound tubulin remnants to exist within the microtubule. We find that these buried GTP remnants enable an alternative mechanism of recovery from shrinkage, and enhances fluctuations of filament lengths. Under conditions for which this alternative mechanism dominates, an increasing depolymerization rate leads to a decrease in dissociation rate and thus a net increase in assembly.

q-bio.BM↗