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Dissertation/Thesis Abstract

Coarse-grained Simulations of Viral Assembly
by Elrad, Oren M., Ph.D., Brandeis University, 2011, 127; 3494429
Abstract (Summary)

The formation of viral capsids is a marvel of natural engineering and design. A large number (from 60 to thousands) of protein subunits assemble into complete, reproducible structures under a variety of conditions while avoiding kinetic and thermodynamic traps. Small single-stranded RNA viruses not only assemble their coat proteins in this fashion but also package their genome during the self-assembly process. Recent experiments have shown that the coat proteins are competent to assemble not merely around their own genomes but heterologous RNA, synthetic polyanions and even functionalized gold nanoparticles. Remarkably these viruses can even assemble around cargo not commensurate with their native state by adopting different morphologies. Understanding the properties that confer such exquisite precision and flexibility to the assembly process could aid biomedical research in the search for novel antiviral remedies, drug-delivery vehicles and contrast agents used in bioimaging. At the same time, viral assembly provides an excellent model system for the development of a statistical mechanical understanding of biological self-assembly, in the hopes of that we will identify some universal principles that underly such processes.

This work consists of computational studies using coarse-grained representations of viral coat proteins and their cargoes. We find the relative strength of protein-cargo and protein-protein interactions has a profound effect on the assembly pathway, in some cases leading to assembly mechanisms that are markedly different from those found in previous work on the assembly of empty capsids. In the case of polymeric cargo, we find the first evidence for a previously theorized mechanism in which the polymer actively participates in recruiting free subunits to the assembly process through cooperative polymer-protein motions. We find that successful assembly is non-monotonic in protein-cargo affinity, such affinity can be detrimental to assembly if it becomes strong enough to stabilize frustrated intermediates that are incompatible with the ground state structure. In cases where the subunits are capable of assembly into different morphologies, we find that maintaining the precise spatial arrangement of subunits seen in the crystal structure is possible even if non-native interactions are disfavored by as little as the thermal energy.

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Indexing (document details)
Advisor: Hagan, Michael F.
Commitee: Dogic, Zvonimir, Miller, Paul
School: Brandeis University
Department: Physics
School Location: United States -- Massachusetts
Source: DAI-B 73/06, Dissertation Abstracts International
Subjects: Condensed matter physics, Virology, Biophysics
Keywords: Coarse-grained Simulations, Self-assembly, Viral assembly, Viruses
Publication Number: 3494429
ISBN: 978-1-267-16219-9
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