Bulletin of the American Physical Society
2009 APS March Meeting
Volume 54, Number 1
Monday–Friday, March 16–20, 2009; Pittsburgh, Pennsylvania
Session T39: Focus Session: Physical Virology |
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Sponsoring Units: DBP Chair: Alex Evilevitch, Lund University Room: 411 |
Wednesday, March 18, 2009 2:30PM - 3:06PM |
T39.00001: Stochastic modeling of virus capsid assembly pathways Invited Speaker: Virus capsids have become a key model system for understanding self-assembly due to their high complexity, robust and efficient assembly processes, and experimental tractability. Our ability to directly examine and manipulate capsid assembly kinetics in detail nonetheless remains limited, creating a need for computer models that can infer experimentally inaccessible features of the assembly process and explore the effects of hypothetical manipulations on assembly trajectories. We have developed novel algorithms for stochastic simulation of capsid assembly [1,2] that allow us to model capsid assembly over broad parameter spaces [3]. We apply these methods to study the nature of assembly pathway control in virus capsids as well as their sensitivity to assembly conditions and possible experimental interventions. \\[4pt] [1] F. Jamalyaria, R. Rohlfs, and R. Schwartz. J Comp Phys 204, 100 (2005). \\[0pt] [2] N. Misra and R. Schwartz. J Chem Phys 129, in press (2008). \\[0pt] [3] B. Sweeney, T. Zhang, and R. Schwartz. Biophys J 94, 772 (2008). [Preview Abstract] |
Wednesday, March 18, 2009 3:06PM - 3:18PM |
T39.00002: How viral capsids adapt to mismatched cargoes—identifying mechanisms of morphology control with simulations Oren Elrad During the replication of many viruses, hundreds to thousands of protein subunits assemble around the viral nucleic acid to form a protein shell called a capsid. Most viruses form one particular structure with astonishing fidelity; yet, recent experiments demonstrate that capsids can assemble with different sizes and morphologies to accommodate nucleic acids or other cargoes such as functionalized nanoparticles. In this talk, we will explore the mechanisms of simultaneous assembly and cargo encapsidation with a computational model that describes the assembly of icosahedral capsids around functionalized nanoparticles. With this model, we find parameter values for which subunits faithfully form empty capsids with a single morphology, but adaptively assemble into different icosahedral morphologies around nanoparticles with different diameters. Analyzing trajectories in which adaptation is or is not successful sheds light on the mechanisms by which capsid morphology may be controlled in vitro and in vivo, and suggests experiments to test these mechanisms. We compare the simulation results to recent experiments in which Brome Mosaic Virus capsid proteins assemble around functionalized nanoparticles, and describe how future experiments can test the model predictions. [Preview Abstract] |
Wednesday, March 18, 2009 3:18PM - 3:30PM |
T39.00003: The role of protein interactions in HIV-1 Capsid Shape and Stability: A Multiscale Analysis Vinod Krishna, Zhiyong Zhang, Wesley I. Sundquist, Chris P. Hill, Gregory A. Voth A coarse grained model of the HIV-1 CA dimer is constructed based on all-atom molecular dynamics simulations of the C-Terminal capsid dimer. Systematic approaches to identify coarse graining sites within the dimer are presented, and the relationship of the coarse grained model parameters to atomistic properties of the capsid discussed. Coarse grained representations of the capsid shell are constructed and their stability examined. The critical importance of an additional carboxyl-hexameric amino terminal interaction is demonstrated. It is shown that this interaction is responsible for generating the curvature of the capsid shell. It is demonstrated that variation of the strength of this interaction for different proteins in the lattice can cause formation of asymmetric, conical shaped closed capsid shells and it is proposed that variations in the structure of the additional carboxyl-amino terminal binding interface during self assembly are critical to capsid cone formation. [Preview Abstract] |
Wednesday, March 18, 2009 3:30PM - 3:42PM |
T39.00004: Mechanisms of viral capsid assembly around a polymer Aleksandr Kivenson, Michael Hagan We present a coarse-grained computational model inspired by the assembly of viral capsid proteins around nucleic acids or other polymers. Specifically, we simulate on a lattice the dynamical assembly of closed, hollow shells composed of several hundred to 1000 subunits, around a flexible polymer. As a function of capsid size, we determine the maximum polymer length that can be dynamically encapsidated and the polymer length around which assembly is most effective. The assembly process can often be described by three phases: nucleation, growth, and a completion phase in which any remaining polymer segments are captured. We find that the polymer can increase the rate of capsid growth by stabilizing the addition of new subunits and by enhancing the incoming flux of subunits. We determine the relative importance of these mechanisms as a function of parameter values, and make predictions for the dependencies of assembly rates and effectiveness on polymer length. These predictions can be tested with bulk experiments in which capsid proteins assemble around nucleic acids or other polymers; in addition, we will discuss how predictions for the polymer-length dependence of assembly rates during the growth phase can be tested with single molecule experiments. [Preview Abstract] |
Wednesday, March 18, 2009 3:42PM - 3:54PM |
T39.00005: Kinetics of human immunodeficiency virus budding and assembly Rui Zhang, Toan Nguyen Human immunodeficiency virus (HIV) belongs to a large family of RNA viruses, retroviruses. Unlike budding of regular enveloped viruses, retroviruses bud \emph{concurrently} with the assembly of retroviral capsids on the cell membrane. The kinetics of HIV (and other retroviruses) budding and assembly is therefore strongly affected by the elastic energy of the membrane and fundamentally different from regular viruses. The main result of this work shows that the kinetics is tunable from a fast budding process to a slow and effectively trapped partial budding process, by varying the attractive energy of retroviral proteins (call Gags), relative to the membrane elastic energy. When the Gag-Gag attraction is relatively high, the membrane elastic energy provides a kinetic barrier for the two pieces of the partial capsids to merge. This energy barrier determines the slowest step in the kinetics and the budding time. In the opposite limit, the membrane elastic energy provides not only a kinetic energy barrier, but a free energy barrier. The budding and assembly is effectively trapped at local free energy minimum, corresponding to a partially budded state. The time scale to escape from this metastable state is exponentially large. In both cases, our result fit with experimental measurements pretty well. [Preview Abstract] |
Wednesday, March 18, 2009 3:54PM - 4:06PM |
T39.00006: Non-equilibrium process of virus shell assembly Artem Levandovsky, Roya Zandi We study non-equilibrium process of a virus outer shell (capsid) formation as a process of self-assembly from identical protein subunits. We model shell growth by attachment of identical subunits resembling triangular prisms with subsequent relaxation of elastic energy. We elucidate the multitude of generic shapes pertinent to larger viruses. Our model predicts formation of not only the basic virus structures such as sphere or cylinder, but also much less explored irregular shapes of retroviruses, such as HIV. The conspicuous conic motif of HIV viruses is shown to appear as realization of one of the two intermediary substates arising as a destruction of symmetry in sphere-to-cylinder transition. The other substate characterized by highly irregular structures is also observed in this work and is consistent with recently reported experimental observations. We construct unified one-dimensional phase diagram that puts spherical, irregular, conical and cylindrical forms in a rather simple perspective of shapes governed by the spontaneous curvature of protein subunits. [Preview Abstract] |
Wednesday, March 18, 2009 4:06PM - 4:18PM |
T39.00007: Exploring the remarkable limits of continuum elastic theory to understand the nanomechanics of viruses Wouter Roos, Melissa Gibbons, William Klug, Gijs Wuite We report nanoindentation experiments by atomic force microscopy on capsids of the Hepatitis B Virus (HBV). HBV is investigated because its capsids can form in either a smaller T=3 or a bigger T=4 configuration, making it an ideal system to test the predictive power of continuum elastic theory to describe nanometre-sized objects. It is shown that for small, consecutive indentations the particles behave reversibly linear and no material fatigue occurs. For larger indentations the particles start to deform non-linearly. The experimental force response fits very well with finite element simulations on coarse grained models of HBV capsids. Furthermore, this also fits with thin shell simulations guided by the F\"{o}ppl- von K\'{a}rm\'{a}n (FvK) number (the dimensionless ratio of stretching and bending stiffness of a thin shell). Both the T=3 and T=4 morphology are very well described by the simulations and the capsid material turns out to have the same Young's modulus, as expected. The presented results demonstrate the surprising strength of continuum elastic theory to describe indentation of viral capsids. [Preview Abstract] |
Wednesday, March 18, 2009 4:18PM - 4:54PM |
T39.00008: to be determined by you Invited Speaker: |
Wednesday, March 18, 2009 4:54PM - 5:06PM |
T39.00009: Conformational changes of Gag HIV-1 on a lipid bilayer measured by neutron reflectivity provides insights into viral particle assembly H. Nanda, S.A.K. Datta, F. Heinrich, M. Loesche, A. Rein, S. Krueger Formation of the HIV-1 is mediated by the Gag polyprotein at the cytoplasmic membrane surface of the infected host cell. Studies suggest large conformational changes in the Gag protein may occur during self-assembly on the membrane [Current Biology, 1997 (7) p.729, J. Mol. Biol. 2007 (365) p. 812]. The one-dimensional profile of Gag bound to a lipid bilayer interface was determined at angstrom resolution by neutron reflectometry. This was done using a novel method for modeling reflectivity data by a Monte Carlo simulation technique. The results show conditions under which the Gag protein can be made to extend or stay compact on the membrane surface. Further atomic detail was obtained using atomistic models to fit the one-dimensional Gag structural data. This involved combining X-ray resolution structures of the ordered protein domains with conformational sampling of the flexible linker region. [Preview Abstract] |
Wednesday, March 18, 2009 5:06PM - 5:18PM |
T39.00010: Assembly of Viruses and the Pseudo Law of Mass Action Alexander Morozov, Robijn Bruinsma, Joseph Rudnick The self-assembly of the protein shell (``capsid'') of a virus is believed to obey the Law of Mass Action (LMA) despite the fact that viral assembly is not a reversible process. In this paper we examine a soluble model for irreversible capsid assembly, the ``Assembly-Line Model.'' We show that, in this model, viral assembly from a supersaturated solution is characterized by a shock front propagating in the assembly configuration space from small to large aggregate sizes. If this shock front is able to reach the size of an assembled capsid, then transient state develops characterized by a ``pseudo'' LMA. This pseudo LMA describes partitioning of capsid proteins between assembled capsids and a metastable, supersaturated solution of free proteins that decays logarithmically slowly. We show that the line energy of assembly intermediates is the key parameter that determines this metastable state. [Preview Abstract] |
Wednesday, March 18, 2009 5:18PM - 5:30PM |
T39.00011: A comparison of the elastic modulii of an animal and plant virus D. Gui, X. Chen, A.L.N. Rao, S. Gill, U. Mohideen, R. Zandi We have used Atomic Force Microscopy (AFM) to image single Sindbis and BMV viruses. The AFM was then used in force spectroscopy mode to measure their elastic Modulii. The similarities and differences will be discussed. [Preview Abstract] |
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