A coarse grain model for DNA.

Understanding the behavior of DNA at the molecular level is of considerable fundamental and engineering importance. While adequate representations of DNA exist at the atomic and continuum level, there is a relative lack of models capable of describing the behavior of DNA at mesoscopic length scales. We present a mesoscale model of DNA that reduces the complexity of a nucleotide to three interactions sites, one each for the phosphate, sugar, and base, thereby rendering the investigation of DNA up to a few microns in length computationally tractable. The charges on these sites are considered explicitly. The model is parametrized using thermal denaturation experimental data at a fixed salt concentration. The validity of the model is established by its ability to predict several aspects of DNA behavior, including salt-dependent melting, bubble formation and rehybridization, and the mechanical properties of the molecule as a function of salt concentration.

[1]  Rodrigo E. Teixeira,et al.  Dynamics of DNA in the flow-gradient plane of steady shear flow: Observations and simulations , 2005 .

[2]  R. Larson,et al.  Brownian dynamics simulations of isolated polymer molecules in shear flow near adsorbing and nonadsorbing surfaces , 2002 .

[3]  S C Harvey,et al.  Action at a distance in supercoiled DNA: effects of sequence on slither, branching, and intramolecular concentration. , 1996, Biophysical journal.

[4]  D. Schwartz,et al.  DNA Molecules in Microfluidic Oscillatory Flow. , 2005, Macromolecules.

[5]  Gregory A Voth,et al.  A coarse-grained model for double-helix molecules in solution: spontaneous helix formation and equilibrium properties. , 2005, The Journal of chemical physics.

[6]  Michel Peyrard.  Nonlinear dynamics and statistical physics of DNA , 2004 .

[7]  Juan J de Pablo,et al.  Shear-induced migration in flowing polymer solutions: simulation of long-chain DNA in microchannels [corrected]. , 2004, The Journal of chemical physics.

[8]  R Lavery,et al.  From atomic to mesoscopic descriptions of the internal dynamics of DNA. , 1999, Biophysical journal.

[9]  S. Harvey,et al.  Molecular mechanics model of supercoiled DNA. , 1989, Journal of molecular biology.

[10]  W. Olson,et al.  Base sequence effects in double‐helical DNA. II. Configurational statistics of rodlike chains , 1988, Biopolymers.

[11]  David Swigon,et al.  Theory of sequence-dependent DNA elasticity , 2003 .

[12]  S. Edwards,et al.  The Theory of Polymer Dynamics , 1986 .

[13]  M. Hao,et al.  Modeling DNA supercoils and knots with B‐spline functions , 1989, Biopolymers.

[14]  S. Harvey,et al.  Molecular dynamics simulations of small DNA plasmids: effects of sequence and supercoiling on intramolecular motions. , 1998, Biopolymers.

[15]  D. Beveridge,et al.  Nucleic acids: theory and computer simulation, Y2K. , 2000, Current opinion in structural biology.

[16]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[17]  P A Kollman,et al.  Molecular dynamics simulation of nucleic acids. , 2000, Annual review of physical chemistry.

[18]  Alexander Vologodskii,et al.  Brownian dynamics simulation of knot diffusion along a stretched DNA molecule. , 2006, Biophysical journal.

[19]  David C. Schwartz,et al.  Effect of confinement on DNA dynamics in microfluidic devices , 2003 .

[20]  D. van der Spoel,et al.  GROMACS: A message-passing parallel molecular dynamics implementation , 1995 .

[21]  Yan Zeng,et al.  Length and statistical weight of bubbles in DNA melting. , 2003, Physical review letters.

[22]  Masakatsu Watanabe,et al.  Dynamics of molecules with internal degrees of freedom by multiple time-step methods , 1993 .

[23]  P. Kollman,et al.  A modified version of the Cornell et al. force field with improved sugar pucker phases and helical repeat. , 1999, Journal of biomolecular structure & dynamics.

[24]  Wilma K Olson,et al.  Sequence-dependent motions of DNA: a normal mode analysis at the base-pair level. , 2002, Biophysical journal.

[25]  Eric S. G. Shaqfeh,et al.  The dynamics of single-molecule DNA in flow , 2005 .

[26]  B. Jacobs.  Serotonin's 50th Anniversary Symposium , 1999, Neuropsychopharmacology.

[27]  Karen Drukker,et al.  A Model for Simulating Dynamics of DNA Denaturation , 2000 .

[28]  M. Record,et al.  Enthalpy and heat capacity changes for formation of an oligomeric DNA duplex: interpretation in terms of coupled processes of formation and association of single-stranded helices. , 1999, Biochemistry.

[29]  Alexander D. MacKerell,et al.  An all-atom empirical energy function for the simulation of nucleic acids , 1995 .

[30]  R. Guimerà,et al.  Mesoscopic modeling for nucleic acid chain dynamics. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[31]  Yan Zeng,et al.  Bubble nucleation and cooperativity in DNA melting. , 2004, Journal of molecular biology.

[32]  R. Swendsen,et al.  THE weighted histogram analysis method for free‐energy calculations on biomolecules. I. The method , 1992 .

[33]  W. Olson,et al.  Base sequence effects in double‐helical DNA. III. Average properties of curved dna , 1988, Biopolymers.

[34]  M. Klein,et al.  Nosé-Hoover chains : the canonical ensemble via continuous dynamics , 1992 .

[35]  Arup K Chakraborty,et al.  Atomistic understanding of kinetic pathways for single base-pair binding and unbinding in DNA , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Lingyan Huang,et al.  Effects of sodium ions on DNA duplex oligomers: improved predictions of melting temperatures. , 2004, Biochemistry.

[37]  Marek Cieplak,et al.  Molecular dynamics of folding of secondary structures in Go-type models of proteins , 1999, cond-mat/9911488.

[38]  B. Pettitt,et al.  Orientation of DNA on a surface from simulation. , 2004, Biopolymers.

[39]  M. Branca.  'Omic diagnostics trip up on way to clinic , 2005, Nature Biotechnology.

[40]  D. Schwartz,et al.  Optical mapping and its potential for large-scale sequencing projects. , 1999, Trends in biotechnology.

[41]  Stephen C Harvey,et al.  Packaging double‐helical DNA into viral capsids , 2004, Biopolymers.

[42]  Thomas E. Cheatham,et al.  Chapter 6 Molecular Modeling and Atomistic Simulation of Nucleic Acids , 2005 .

[43]  Heinz Sklenar,et al.  Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. II: sequence context effects on the dynamical structures of the 10 unique dinucleotide steps. , 2005, Biophysical journal.

[44]  S. Smith,et al.  Ionic effects on the elasticity of single DNA molecules. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[45]  P. Hagerman.  Flexibility of DNA. , 1988, Annual review of biophysics and biophysical chemistry.

[46]  Jiyoung Heo,et al.  Atomic-level simulations of seeman DNA nanostructures: the paranemic crossover in salt solution. , 2006, Biophysical journal.

[47]  S. Harvey,et al.  Molecular modeling of closed circular DNA thermodynamic ensembles. , 1998, Biopolymers.

[48]  C. Bustamante,et al.  Overstretching B-DNA: The Elastic Response of Individual Double-Stranded and Single-Stranded DNA Molecules , 1996, Science.

[49]  Juan J. de Pablo,et al.  Stochastic simulations of DNA in flow: Dynamics and the effects of hydrodynamic interactions , 2002 .

[50]  Berk Hess,et al.  GROMACS 3.0: a package for molecular simulation and trajectory analysis , 2001 .

[51]  Thomas E Cheatham,et al.  Simulation and modeling of nucleic acid structure, dynamics and interactions. , 2004, Current opinion in structural biology.

[52]  T. Ha,et al.  Probing single-stranded DNA conformational flexibility using fluorescence spectroscopy. , 2004, Biophysical journal.

[53]  Alessandro Flammini,et al.  Simulations of action of DNA topoisomerases to investigate boundaries and shapes of spaces of knots. , 2004, Biophysical journal.