Chemically accurate coarse graining of double-stranded DNA

Coarse-grained (CG) modeling approaches are widely used to simulate many important biological processes involving DNA, including chromatin folding and genomic packaging. The bending propensity of a semiflexible DNA molecule critically influences these processes. However, existing CG DNA models do not retain a sufficient fidelity of the important local chain motions, whose propagation at larger length scales would generate correct DNA persistent lengths, in particular when the solution’s ionic strength is widely varied. Here we report on a development of an accurate CG model for the double-stranded DNA chain, with explicit treatment of mobile ions, derived systematically from all-atom molecular dynamics simulations. Our model generates complex local motions of the DNA chain, similar to fully atomistic dynamics, leading also to a quantitative agreement of our simulation results with the experimental data on the dependence of the DNA persistence length on the solution ionic strength. We also predict a structural transition in a torsionally stressed DNA nanocircle as the buffer ionic strength is increased beyond a threshold value.

[1]  J. Weeks,et al.  Local molecular field theory for effective attractions between like charged objects in systems with strong Coulomb interactions , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[2]  C. Laughton,et al.  Mapping the phase diagram of the writhe of DNA nanocircles using atomistic molecular dynamics simulations , 2007, Nucleic acids research.

[3]  J. Zinn-Justin.  Quantum Field Theory and Critical Phenomena , 2002 .

[4]  R. Swendsen.  Monte Carlo Renormalization Group , 2011 .

[5]  J. Schellman,et al.  Flow dichroism of T7 DNA as a function of salt concentration , 1981, Biopolymers.

[6]  B. Shklovskii.  WIGNER CRYSTAL MODEL OF COUNTERION INDUCED BUNDLE FORMATION OF RODLIKE POLYELECTROLYTES , 1998, cond-mat/9809429.

[7]  Alexey Savelyev,et al.  Molecular renormalization group coarse-graining of polymer chains: application to double-stranded DNA. , 2009, Biophysical journal.

[8]  J. Zlatanova,et al.  Nucleosome assembly depends on the torsion in the DNA molecule: a magnetic tweezers study. , 2009, Biophysical journal.

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

[10]  Alexey Savelyev,et al.  Molecular renormalization group coarse-graining of electrolyte solutions: application to aqueous NaCl and KCl. , 2009, The journal of physical chemistry. B.

[11]  J. Langowski.  Polymer chain models of DNA and chromatin , 2006, The European physical journal. E, Soft matter.

[12]  Cecilia Clementi,et al.  Minimalist protein model as a diagnostic tool for misfolding and aggregation. , 2006, Journal of molecular biology.

[13]  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.

[14]  G. Papoian,et al.  Inter-DNA electrostatics from explicit solvent molecular dynamics simulations. , 2007, Journal of the American Chemical Society.

[15]  Gregory A. Voth,et al.  The multiscale coarse-graining method. I. A rigorous bridge between atomistic and coarse-grained models. , 2008, The Journal of chemical physics.

[16]  Q. Cui,et al.  A computational framework for mechanical response of macromolecules: application to the salt concentration dependence of DNA bendability. , 2009, Biophysical journal.

[17]  Michael L. Klein,et al.  Coarse grain models and the computer simulation of soft materials , 2004 .

[18]  K. Besteman,et al.  Charge inversion at high ionic strength studied by streaming currents. , 2006, Physical review letters.

[19]  G. Papoian,et al.  Polyionic charge density plays a key role in differential recognition of mobile ions by biopolymers. , 2008, The journal of physical chemistry. B.

[20]  D. Schwartz,et al.  A coarse grain model for DNA. , 2007, The Journal of chemical physics.

[21]  Kelly M. Thayer,et al.  Ion motions in molecular dynamics simulations on DNA. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Changbong Hyeon,et al.  Charge density of divalent metal cations determines RNA stability. , 2007, Journal of the American Chemical Society.

[23]  Charles L. Brooks,et al.  Insights from Coarse-Grained Gō Models for Protein Folding and Dynamics , 2009, International journal of molecular sciences.

[24]  P. Hagerman,et al.  Investigation of the flexibility of DNA using transient electric birefringence , 1981, Biopolymers.

[25]  G. Papoian,et al.  Electrostatic, steric, and hydration interactions favor Na(+) condensation around DNA compared with K(+). , 2006, Journal of the American Chemical Society.

[26]  Alexander Schug,et al.  Nonlocal helix formation is key to understanding S-adenosylmethionine-1 riboswitch function. , 2009, Biophysical journal.

[27]  Tamar Schlick,et al.  Flexible histone tails in a new mesoscopic oligonucleosome model. , 2006, Biophysical journal.

[28]  A. Lyubartsev,et al.  Calculation of effective interaction potentials from radial distribution functions: A reverse Monte Carlo approach. , 1995, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[29]  J. Šponer,et al.  Refinement of the AMBER Force Field for Nucleic Acids: Improving the Description of α/γ Conformers , 2007 .

[30]  Daniel Svozil,et al.  Refinement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. , 2007, Biophysical journal.

[31]  T. Cheatham,et al.  Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations , 2008, The journal of physical chemistry. B.

[32]  S. P. Mielke,et al.  Brownian dynamics of double-stranded DNA in periodic systems with discrete salt. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[33]  A. Mazur.  Evaluation of elastic properties of atomistic DNA models. , 2006, Biophysical journal.

[34]  J. Onuchic,et al.  Topological and energetic factors: what determines the structural details of the transition state ensemble and "en-route" intermediates for protein folding? An investigation for small globular proteins. , 2000, Journal of molecular biology.

[35]  Changbong Hyeon,et al.  Theoretical perspectives on protein folding. , 2010, Annual review of biophysics.