Molecular Dynamics Simulations of a Nucleosome and Free DNA

Abstract All atom molecular dynamics simulations (10ns) of a nucleosome and of its 146 basepairs of DNA free in solution have been conducted. DNA helical parameters (Roll, Tilt, Twist, Shift, Slide, Rise) were extracted from each trajectory to compare the conformation, effective force constants, persistence length measures, and fluctuations of nucleosomal DNA to free DNA. The conformation of DNA in the nucleosome, as determined by helical parameters, is found to be largely within the range of thermally accessible values obtained for free DNA. DNA is found to be less flexible on the nucleosome than when free in solution, however such measures are length scale dependent. A method for disassembling and reconstructing the conformation and dynamics of the nucleosome using Fourier analysis is presented. Long length variations in the conformation of nucleosomal DNA are identified other than those associated with helix repeat. These variations are required to create a proposed tetrasome conformation or to qualitatively reconstruct the 1.75 turns of the nucleosome's superhelix. Reconstruction of free DNA using selected long wavelength variations in conformation can produce either a left-handed or a right-handed superhelix. The long wavelength variations suggest 146 basepairs is a natural length of DNA to wrap around the histone core.

[1]  W. Olson,et al.  3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. , 2003, Nucleic acids research.

[2]  J. HeyrovskyInstitute.  Sequence-dependent Elastic Properties of DNA , 2000 .

[3]  A. Sivolob,et al.  Nucleosome conformational flexibility and implications for chromatin dynamics , 2004, Philosophical Transactions of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences.

[4]  Peter A. Kollman,et al.  AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules , 1995 .

[5]  J. Léger,et al.  Structural Transitions of a Twisted and Stretched DNA Molecule , 1999 .

[6]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[7]  R. Kornberg.  Chromatin structure: a repeating unit of histones and DNA. , 1974, Science.

[8]  T. Richmond,et al.  Crystals of a nucleosome core particle containing defined sequence DNA. , 1988, Journal of molecular biology.

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

[10]  Steven G. Johnson,et al.  FFTW: an adaptive software architecture for the FFT , 1998, Proceedings of the 1998 IEEE International Conference on Acoustics, Speech and Signal Processing, ICASSP '98 (Cat. No.98CH36181).

[11]  R. Dickerson,et al.  Definitions and nomenclature of nucleic acid structure components. , 1989, Nucleic acids research.

[12]  T. Bishop,et al.  POTENTIAL FUNCTION DESCRIBING THE FOLDING OF THE 30 NM FIBER , 1998 .

[13]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[14]  Jörg Langowski,et al.  DNA basepair step deformability inferred from molecular dynamics simulations. , 2003, Biophysical journal.

[15]  J. Langowski,et al.  Critical effect of the N2 amino group on structure, dynamics, and elasticity of DNA polypurine tracts. , 2002, Biophysical journal.

[16]  Laxmikant V. Kale,et al.  NAMD2: Greater Scalability for Parallel Molecular Dynamics , 1999 .

[17]  J. Hearst,et al.  The Kirchhoff elastic rod, the nonlinear Schrödinger equation, and DNA supercoiling , 1994 .

[18]  D. Timm,et al.  Asymmetries in the nucleosome core particle at 2.5 A resolution. , 2000, Acta crystallographica. Section D, Biological crystallography.

[19]  E. Uberbacher,et al.  X-ray diffraction analysis of crystals containing twofold symmetric nucleosome core particles. , 1996, Acta crystallographica. Section D, Biological crystallography.

[20]  G. Arents,et al.  Topography of the histone octamer surface: repeating structural motifs utilized in the docking of nucleosomal DNA. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Noll.  Subunit structure of chromatin , 1974, Nature.

[22]  A. Prunell.  A topological approach to nucleosome structure and dynamics: the linking number paradox and other issues. , 1998, Biophysical journal.

[23]  J. Maddocks,et al.  A Continuum Rod Model of Sequence-Dependent DNA Structure , 1996 .

[24]  T. Richmond,et al.  Solvent mediated interactions in the structure of the nucleosome core particle at 1.9 a resolution. , 2002, Journal of molecular biology.

[25]  S. Khorasanizadeh.  The Nucleosome From Genomic Organization to Genomic Regulation , 2004, Cell.

[26]  T. Richmond,et al.  The structure of DNA in the nucleosome core , 2003, Nature.

[27]  John F. Marko,et al.  Introduction to Single-DNA Micromechanics , 2005 .

[28]  A J Koster,et al.  Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Ricardo Cortez,et al.  Investigation of bend and shear waves in a geometrically exact elastic rod model , 2004 .

[30]  J. Hearst,et al.  Elastic rod model incorporating shear and extension, generalized nonlinear Schrödinger equations, and novel closed‐form solutions for supercoiled DNA , 1995 .

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

[32]  R. Kornberg,et al.  Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome , 1999, Cell.

[33]  J. Widom,et al.  Role of DNA sequence in nucleosome stability and dynamics , 2001, Quarterly Reviews of Biophysics.