Structural deformations of DNA play a central role in many biological processes, including gene expression. The structural deformations are sensitive to the material properties of the molecule, and these, in turn, vary along the molecule’s length according to its base-pair sequence. Examples of “sequence-dependent” material properties include the stress-free curvature and the stiffness for bending and torsion. Quantifying and separating these sequence-dependent properties from experimental data remains a significant challenge as they often work in unison in nature. In this paper, we offer a method for resolving and quantifying the sequence-dependent stiffness of DNA from cyclization (loop closure) experiments using a computational rod model of the molecule.
Issue Section:
Research Papers
1.
Calladine
, C. R.
, Drew
, H. R.
, Luisi
, B. F.
, and Travers
, A. A.
, 2004, Understanding DNA, the Molecule and How It Works
, Elsevier Academic
, Amsterdam
.2.
Branden
, C.
, and Tooze
, J.
, 1999, Introduction to Protein Structure
, Garland
, New York
.3.
Lehninger
, A. L.
, Nelson
, D. L.
, and Cox
, M. M.
, 2005, Lehninger Principles of Biochenistry
, Freeman
, New York
.4.
Franklin
, R. E.
, and Gosling
, R. G.
, 1953, “Molecular Configuration in Sodium Thymonucleate
,” Nature (London)
0028-0836, 171
(4356
), pp. 740
–741
.5.
Watson
, J. D.
, and Crick
, F. H. C.
, 1953, “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid
,” Nature (London)
0028-0836, 171
(4356
), pp. 737
–738
.6.
Schleif
, R.
, 1992, “DNA Looping
,” Annu. Rev. Biochem.
0066-4154, 61
, pp. 199
–223
.7.
Semsey
, S.
, Virnik
, K.
, and Adhya
, S.
, 2005, “A Gamut of Loops: Meandering DNA
,” Trends Biochem. Sci.
0167-7640, 30
(6
), pp. 334
–341
.8.
Goyal
, S.
, Lillian
, T.
, Blumberg
, S.
, Meiners
, J. C.
, Meyhofer
, E.
, and Perkins
, N. C.
, 2007, “Intrinsic Curvature of DNA Influences LacR-Mediated Looping
,” Biophys. J.
0006-3495, 93
(12
), in press.9.
Goyal
, S.
, 2006, “A Dynamic Rod Model to Simulate Mechanics of Cables and DNA
,” Ph.D. thesis, Mechanical Engineering, University of Michigan, Ann Arbor.10.
Schlick
, T.
, 1995, “Modeling Superhelical DNA: Recent Analytical and Dynamic Approaches
,” Curr. Opin. Struct. Biol.
0959-440X, 5
(2
), pp. 245
–262
.11.
Olson
, W. K.
, 1996, “Simulating DNA at Low Resolution
,” Curr. Opin. Struct. Biol.
0959-440X, 6
(2
), pp. 242
–256
.12.
Goyal
, S.
, Lillian
, T.
, Perkins
, N. C.
, and Meyhofer
, E.
, 2005, “Cable Dynamics Applied to Long-Length Scale Mechanics of DNA
,” CD-ROM Proceedings of Sixth International Symposium of Cable Dynamics
, Chaleston, SC
.13.
Kehrbaum
, S.
, and Maddocks
, J. H.
, 2000, “Effective Properties of Elastic Rods With High Intrinsic Twist
,” 16th IMACS World Congress
.14.
Rey
, S.
, and Maddocks
, J. H.
, 2000, “Buckling of an Elastic Rod With High Intrinsic Twist
,” 16th IMACS World Congress
.15.
Goyal
, S.
, Perkins
, N. C.
, and Lee
, C. L.
, 2005, “Nonlinear Dynamics and Loop Formation in Kirchhoff Rods with Implications to the Mechanics of DNA and Cables
,” J. Comput. Phys.
0021-9991, 209
(1
), pp. 371
–389
.16.
Manning
, R. S.
, Maddocks
, J. H.
, and Kahn
, J. D.
, 1996, “A Continuum Rod Model of Sequence-Dependent DNA Structure
,” J. Chem. Phys.
0021-9606, 105
(13
), pp. 5626
–5646
.17.
Beveridge
, D. L.
, Barreiro
, G.
, Byun
, K. S.
, Case
, D. A.
, Cheatham
, T. E.
, Dixit
, S. B.
, Giudice
, E.
, Lankas
, F.
, Lavery
, R.
, Maddocks
, J. H.
, Osman
, R.
, Seibert
, E.
, Sklenar
, H.
, Stoll
, G.
, Thayer
, K. M.
, Varnai
, P.
, and Young
, M. A.
, 2004, “Molecular Dynamics Simulations of the 136 Unique Tetranucleotide Sequences of DNA Oligonucleotides. I. Research Design and Results on D(C(P)G) Steps
,” Biophys. J.
0006-3495, 87
(6
), pp. 3799
–3813
.18.
Dixit
, S. B.
, Beveridge
, D. L.
, Case
, D. A.
, Cheatham
, T. E.
, Giudice
, E.
, Lankas
, F.
, Lavery
, R.
, Maddocks
, J. H.
, Osman
, R.
, Sklenar
, H.
, Thayer
, K. M.
, and Varnai
, P.
, 2005, “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
,” Biophys. J.
0006-3495, 89
(6
), pp. 3721
–3740
.19.
Cloutier
, T. E.
, and Widom
, J.
, 2004, “Spontaneous Sharp Bending of Double-Stranded DNA
,” Mol. Cell
1097-2765, 14
(3
), pp. 355
–362
.20.
Du
, Q.
, Smith
, C.
, Shiffeldrim
, N.
, Vologodskaia
, M.
, and Vologodskii
, A.
, 2005, “Cyclization of Short DNA Fragments and Bending Fluctuations of the Double Helix
,” Proc. Natl. Acad. Sci. U.S.A.
0027-8424, 102
(15
), pp. 5397
–5402
.21.
Wiggins
, P. A.
, Phillips
, R.
, and Nelson
, P. C.
, 2005, “Exact Theory of Kinkable Elastic Polymers
,” Phys. Rev. E
1063-651X, 71
(2
), p. 021909
.22.
Mehta
, R. A.
, and Kahn
, J. D.
, 1999, “Designed Hyperstable Lac Repressor-DNA Loop Topologies Suggest Alternative Loop Geometries
,” J. Mol. Biol.
0022-2836, 294
(1
), pp. 67
–77
.23.
Morgan
, M. A.
, Okamoto
, K.
, Kahn
, J. D.
, and English
, D. S.
, 2005, “Single-Molecule Spectroscopic Determination of Lac Repressor-DNA Loop Conformation
,” Biophys. J.
0006-3495, 89
(4
), pp. 2588
–2596
.24.
Chung
, J.
, and Hulbert
, G. M.
, 1993, “A Time Integration Algorithm for Structural Dynamics With Improved Numerical Dissipation: The Generalized-Alpha Method
,” Trans. ASME, J. Appl. Mech.
0021-8936, 60
(2
), pp. 371
–375
.25.
Gobat
, J. I.
, and Grosenbaugh
, M. A.
, 2001, “Application of the Generalized-Alpha Method to the Time Integration of the Cable Dynamics Equations
,” Comput. Methods Appl. Mech. Eng.
0045-7825, 190
(37-38
), pp. 4817
–4829
.26.
Gobat
, J. I.
, Grosenbaugh
, M. A.
, and Triantafyllou
, M. S.
, 2002, “Generalized-Alpha Time Integration Solutions for Hanging Chain Dynamics
,” J. Eng. Mech.
0733-9399, 128
(6
), pp. 677
–687
.27.
Shimada
, J.
, and Yamakawa
, H.
, 1984, “Ring-Closure Probabilities for Twisted Wormlike Chains: Application to DNA
,” Macromolecules
0024-9297, 17
(4
), pp. 689
–698
.28.
Zhang
, Y. L.
, and Crothers
, D. M.
, 2003, “Statistical Mechanics of Sequence-Dependent Circular DNA and Its Application for DNA Cyclization
,” Biophys. J.
0006-3495, 84
(1
), pp. 136
–153
.29.
Popov
, Y. O.
, and Tkachenko
, A. V.
, 2005, “Effects of Kinks on DNA Elasticity
,” Phys. Rev. E
1063-651X, 71
(5
), p. 051905
.30.
Wilson
, D. P.
, Lillian
, T. D.
, Goyal
, S.
, Perkins
, N. C.
, Tkachenko
, A.
, and Meiners
, J. C.
, 2007, “Modeling the Entropic Cost of DNA Looping
,” Biophys. J.
0006-3495, p. 540A
; available at: http://www.biophysics.org/abstracts/31.
Howard
, J.
, 2001, Mechanics of Motor Proteins and the Cytoskeleton
, Sinauer Associates
, Sunderland
.32.
Hagerman
, P. J.
, 1988, “Flexibility of DNA
,” Annu. Rev. Biophys. Biophys. Chem.
0883-9182, 17
, pp. 265
–286
.33.
Gabrielian
, A.
, and Pongor
, S.
, 1996, “Correlation of Intrinsic DNA Curvature With DNA Property Periodicity
,” FEBS Lett.
0014-5793, 393
(1
), pp. 65
–68
.34.
Weaver
, R.
, 2007, Molecular Biology
, McGraw-Hill
, Boston
.35.
Baumann
, C. G.
, Smith
, S. B.
, Bloomfield
, V. A.
, and Bustamante
, C.
, 1997, “Ionic Effects on the Elasticity of Single DNA Molecules
,” Proc. Natl. Acad. Sci. U.S.A.
0027-8424, 94
(12
), pp. 6185
–6190
.36.
Strick
, T. R.
, Allemand
, J. F.
, Bensimon
, D.
, Bensimon
, A.
, and Croquette
, V.
, 1996, “The Elasticity of a Single Supercoiled DNA Molecule
,” Science
0036-8075, 271
(5257
), pp. 1835
–1837
.37.
Balaeff
, A.
, Mahadevan
, L.
, and Schulten
, K.
, 2006, “Modeling DNA Loops Using the Theory of Elasticity
,” Phys. Rev. E
1063-651X, 73
(3
), p. 031919
.Copyright © 2008
by American Society of Mechanical Engineers
You do not currently have access to this content.
