Modeling Viral Capsid Modeling Viral Capsid AssemblyAssembly

Rajar ManoharanRajar Manoharan

The Hagan Laboratory at Brandeis University

Introduction to the Hagan LabIntroduction to the Hagan LabOverarching goal:Overarching goal: Understand the way Understand the way

that viruses replicate that viruses replicate using computer using computer modeling. modeling.

Implications of this work: Implications of this work: If we understand how If we understand how

viruses construct new viruses construct new viruses, we will be closer viruses, we will be closer to preventing viral to preventing viral infection.infection.

If we understand how If we understand how viruses deliver RNA/DNA, viruses deliver RNA/DNA, we can design drug we can design drug delivery systems.delivery systems.

Dr. Michael Hagan

Hepatitis B Virus

What is a capsid?What is a capsid?• Protein “shell” of virus that Protein “shell” of virus that

encloses viral genetic encloses viral genetic material (either DNA or material (either DNA or RNA)RNA)

• 50-90% of virus50-90% of virus• Three main functions: Three main functions:

protect nucleic acids, protect nucleic acids, identify target cells , identify target cells , release viral genomerelease viral genome

• Can be helical, icosahedral, Can be helical, icosahedral, dodecahedral, etc.dodecahedral, etc.

• Specific target of modelingSpecific target of modeling

BMV Capsid

Hepatitis C Virus

Tools Used and Day to Day WorkTools Used and Day to Day Work

Hagan and Chandler, 2006

b5

triangles

trapezoids

Oren Elrad

Statistical MechanicsStatistical Mechanics ThermodynamicsThermodynamics Desktop PC, Brandeis High Desktop PC, Brandeis High

Performance Computing Performance Computing Cluster, C++, UnixCluster, C++, Unix

Ran simulationsRan simulations Wolfram MathematicaWolfram Mathematica Studied the effect of Studied the effect of

subunit geometry on subunit geometry on assemblyassembly

Compared and contrasted Compared and contrasted triangles, trapezoids, b3b, triangles, trapezoids, b3b, b5 modelsb5 models

DiscussionDiscussion

More complex More complex geometries: geometries:

2)2) Assemble more slowly Assemble more slowly 3)3) Produce fewer Produce fewer

malformed capsids malformed capsids 4)4) More abrupt changes More abrupt changes

in rate of assemblyin rate of assembly Slower assembly more Slower assembly more

successfulsuccessful

Slow assembly

Fast assembly

OutlookOutlook HIV, H1N1, EbolaHIV, H1N1, Ebola What is the role of What is the role of

the membrane in the membrane in assembly?assembly?

Account for nucleic Account for nucleic acid core, acid core, scaffoldingscaffolding

Unique geometriesUnique geometries Viral evolutionViral evolution

HIV

Influenza

www.virology.net/Big_Virology/BVRNAortho.html

http://www.aids-info.ch