Molecular dynamics/order parameter extrapolation for bionanosystem simulations

A multiscale approach, molecular dynamics/order parameter extrapolation (MD/OPX), to the all‐atom simulation of large bionanosystems is presented. The approach starts with the introduction of a set of order parameters (OPs) automatically generated with orthogonal polynomials to characterize the nanoscale features of bionanosystems. The OPs are shown to evolve slowly via Newton's equations, and the all‐atom multiscale analysis (AMA) developed earlier (Miao and Ortoleva, J Chem Phys 2006, 125, 44901) demonstrates the existence of their stochastic dynamics, which serve as the justification for our MD/OPX approach. In MD/OPX, a short MD run estimates the rate of change of the OPs, which is then used to extrapolate the state of the system over time that is much longer than the 10−14 second timescale of fast atomic vibrations and collisions. The approach is implemented in NAMD and demonstrated on cowpea chlorotic mottle virus (CCMV) capsid structural transitions (STs). It greatly accelerates the MD code and its underlying all‐atom description of the nanosystems enables the use of a universal interatomic force field, avoiding recalibration with each new application as needed for coarse‐grained models. The source code of MD/OPX is distributed free of charge at https://simtk.org/home/mdopx and a web portal will be available via http://sysbio.indiana.edu/virusx. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009

[1]  John E. Johnson,et al.  Cooperative reorganization of a 420 subunit virus capsid. , 2005, Journal of molecular biology.

[2]  J. Hogle,et al.  Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding , 1990, Journal of virology.

[3]  Mark E. Tuckerman,et al.  Molecular dynamics algorithm for multiple time scales: Systems with long range forces , 1991 .

[4]  C. Post,et al.  A novel basis of capsid stabilization by antiviral compounds. , 1995, Journal of molecular biology.

[5]  J. Hogle,et al.  Kinetic Analysis of the Effect of Poliovirus Receptor on Viral Uncoating: the Receptor as a Catalyst , 2001, Journal of Virology.

[6]  Herschel Rabitz,et al.  Subspace Method for Long Time Scale Molecular Dynamics , 1995 .

[7]  John E. Johnson,et al.  Structures of the native and swollen forms of cowpea chlorotic mottle virus determined by X-ray crystallography and cryo-electron microscopy. , 1995, Structure.

[8]  J. Hogle.  Poliovirus cell entry: common structural themes in viral cell entry pathways. , 2002, Annual review of microbiology.

[9]  Peter J. Ortoleva,et al.  Curvilinear All-Atom Multiscale (CAM) Theory of Macromolecular Dynamics , 2008 .

[10]  J. Durup.  Protein molecular dynamics constrained to slow modes: theoretical approach based on a hierarchy of local modes with a set of holonomic constraints; the method and its tests on citrate synthase , 1991 .

[11]  Yves-Henri Sanejouand,et al.  Modal dynamics of proteins in water , 2000 .

[12]  Peter L. Freddolino,et al.  Molecular dynamics simulations of the complete satellite tobacco mosaic virus. , 2006, Structure.

[13]  B. Brooks,et al.  Molecular dynamics simulations of human rhinovirus and an antiviral compound. , 2001, Biophysical journal.

[14]  B L Trus,et al.  Three-dimensional structure of poliovirus receptor bound to poliovirus. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  John E. Johnson,et al.  Large-Scale, pH-Dependent, Quaternary Structure Changes in an RNA Virus Capsid Are Reversible in the Absence of Subunit Autoproteolysis , 2002, Journal of Virology.

[16]  Peter Ortoleva,et al.  All-atom multiscaling and new ensembles for dynamical nanoparticles. , 2006, The Journal of chemical physics.

[17]  C. Brooks,et al.  Diversity and identity of mechanical properties of icosahedral viral capsids studied with elastic network normal mode analysis. , 2005, Journal of molecular biology.

[18]  H. Tsuruta,et al.  Analysis of rapid, large-scale protein quaternary structural changes: time-resolved X-ray solution scattering of Nudaurelia capensis omega virus (NomegaV) maturation. , 2001, Journal of molecular biology.

[19]  Alasdair C. Steven,et al.  Molecular Tectonic Model of Virus Structural Transitions: the Putative Cell Entry States of Poliovirus , 2000, Journal of Virology.

[20]  Laxmikant V. Kalé,et al.  Scalable molecular dynamics with NAMD , 2005, J. Comput. Chem..

[21]  John E. Johnson,et al.  Large conformational changes in the maturation of a simple RNA virus, Nudaurelia capensis ω virus (NωV). , 2000 .

[22]  Sebastian Reich,et al.  Smoothed dynamics of highly oscillatory Hamiltonian systems , 1995 .

[23]  P. Rossky,et al.  Influence of an antiviral compound on the temperature dependence of viral protein flexibility and packing: a molecular dynamics study. , 1998, Journal of molecular biology.

[24]  Martin Karplus,et al.  Normal mode calculations of icosahedral viruses with full dihedral flexibility by use of molecular symmetry. , 2005, Journal of molecular biology.

[25]  John E. Johnson,et al.  Time-resolved molecular dynamics of bacteriophage HK97 capsid maturation interpreted by electron cryo-microscopy and X-ray crystallography. , 2006, Journal of structural biology.

[26]  Yinglong Miao,et al.  Viral structural transitions: an all-atom multiscale theory. , 2006, The Journal of chemical physics.

[27]  Mark E. Tuckerman,et al.  Molecular dynamics in systems with multiple time scales: Systems with stiff and soft degrees of freedom and with short and long range forces , 1991 .

[28]  Khuloud Jaqaman,et al.  New space warping method for the simulation of large‐scale macromolecular conformational changes , 2002, J. Comput. Chem..

[29]  Florence Tama,et al.  The mechanism and pathway of pH induced swelling in cowpea chlorotic mottle virus. , 2002, Journal of molecular biology.

[30]  John E. Johnson,et al.  Pseudo-atomic models of swollen CCMV from cryo-electron microscopy data. , 2003, Journal of structural biology.

[31]  John E. Johnson,et al.  Enhanced Local Symmetry Interactions Globally Stabilize a Mutant Virus Capsid That Maintains Infectivity and Capsid Dynamics , 2006, Journal of Virology.

[32]  Y. Sanejouand,et al.  Modeling large-scale dynamics of proteins. , 1998, Biopolymers.

[33]  Ioannis G. Kevrekidis,et al.  Equation-free: The computer-aided analysis of complex multiscale systems , 2004 .

[34]  W. Gelbart,et al.  Structure, stability, and thermodynamics of lamellar DNA-lipid complexes. , 1998, Biophysical journal.

[35]  M. Karplus,et al.  Normal mode analysis of large systems with icosahedral symmetry: Application to (Dialanine)60 in full and reduced basis set implementations , 2001 .

[36]  Klaus Schulten,et al.  Stability and dynamics of virus capsids described by coarse-grained modeling. , 2006, Structure.

[37]  Berk Hess,et al.  Improving efficiency of large time‐scale molecular dynamics simulations of hydrogen‐rich systems , 1999, Journal of computational chemistry.

[38]  Carlos E. Padilla,et al.  MBO(N)D: A multibody method for long‐time molecular dynamics simulations , 2000 .

[39]  A. Voter,et al.  Temperature-accelerated dynamics for simulation of infrequent events , 2000 .

[40]  John E. Johnson,et al.  Quasi-equivalent viruses: a paradigm for protein assemblies. , 1997, Journal of molecular biology.

[41]  Trevor Douglas,et al.  Structural transitions in Cowpea chlorotic mottle virus (CCMV) , 2005, Physical biology.