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dc.contributor.advisor Ortoleva, Peter J en_US Miao, Yinglong en_US 2010-06-16T17:42:10Z 2012-03-23T21:30:49Z 2012-03-23T21:32:51Z 2010-06-16T17:42:10Z 2009 en_US
dc.description Thesis (Ph.D.) - Indiana University, Chemistry, 2009 en_US
dc.description.abstract Viruses are composed of millions of atoms functioning on supra-nanometer length scales over timescales of milliseconds or greater. In contrast, individual atoms interact on scales of angstroms and femtoseconds. Thus they display dual microscopic/macroscopic characteristics involving processes that span across widely-separated time and length scales. To address this challenge, we introduced automatically generated collective modes and order parameters to capture viral large-scale low-frequency coherent motions. With an all-atom multiscale analysis (AMA) of the Liouville equation, a stochastic (Fokker-Planck or Smoluchowski) equation and equivalent Langevin equations are derived for the order parameters. They are shown to evolve on timescales much larger than the 10^(-14)-second timescale of fast atomistic vibrations and collisions. This justifies a novel multiscale Molecular Dynamics/Order Parameter eXtrapolation (MD/OPX) approach, which propagates viral atomistic and nanoscale dynamics simultaneously by solving the Langevin equations of order parameters implicitly without the need to construct thermal-average forces and friction/diffusion coefficients. In MD/OPX, a set of short replica MD runs with random atomic velocity initializations estimate the ensemble average rate of change in order parameters, extrapolation of which is then used to project the system over long time. The approach was implemented by using NAMD as the MD platform. Application of MD/OPX to cowpea chlorotic mottle virus (CCMV) capsid revealed that its swollen state undergoes significant energy-driven shrinkage in vacuum during 200ns simulation, while for the native state as solvated in a host medium at pH 7.0 and ionic strength I=0.2M, the N-terminal arms of capsid proteins are shown to be highly dynamic and their fast fluctuations trigger global expansion of the capsid. Viral structural transitions associated with both processes are symmetry-breaking involving local initiation and front propagation. MD/OPX accelerates MD for long-time simulation of viruses, as well as other large bionanosystems. By using universal inter-atomic force fields, it is generally applicable to all dynamical nanostructures and avoids the need of parameter recalibration with each new application. With our AMA method and MD/OPX, viral dynamics are predicted from laws of molecular physics via rigorous statistical mechanics. en_US
dc.language.iso EN en_US
dc.publisher [Bloomington, Ind.] : Indiana University en_US
dc.subject cowpea chlorotic mottle virus en_US
dc.subject collective modes en_US
dc.subject structural transitions en_US
dc.subject molecular dynamics/order parameter extrapolation en_US
dc.subject all-atom multiscale analysis en_US
dc.subject viral dynamics en_US
dc.subject.classification Chemistry, Physical en_US
dc.subject.classification Biology, Virology en_US
dc.subject.classification Biophysics, General en_US
dc.title All-Atom Multiscale Computational Modeling Of Viral Dynamics en_US
dc.type Doctoral Dissertation en_US

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