Molecular modelling of (A4T4NN)n and (T4A4NN)n: sequence elements responsible for curvature.

The molecular modelling program JUMNA has been used to investigate the origins of the strikingly different curvature of the two sequences, (A4T4NN)n and (T4A4NN)n. Gel electrophoresis and cyclisation studies have shown that only the former of these two sequences is significantly curved. By developing novel superhelical symmetry constraints we were able to study the energetic and structural aspects of polymeric DNA having a controlled curvature. The results obtained (which do not take into account specific hydration effects) correlate well with the experimental data and offer a molecular level explanation of curvature. Although curvature is found to be initiated by specific dinucleotide junctions, deformations spread to surrounding dinucleotide steps and, moreover, sequence effects beyond the dinucleotide level are observed.

[1]  D. Crothers,et al.  Structural basis for DNA bending. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[2]  E. Westhof,et al.  Three-center hydrogen bonds in DNA: molecular dynamics of poly(dA).cntdot.poly(dT) , 1991 .

[3]  P. Hagerman,et al.  Sequence-directed curvature of DNA. , 1986, Nature.

[4]  R. Wells,et al.  Unusual DNA Structures , 2011, Springer New York.

[5]  P. Hagerman.  Pyrimidine 5-methyl groups influence the magnitude of DNA curvature. , 1990, Biochemistry.

[6]  D. Crothers,et al.  Calibration of DNA curvature and a unified description of sequence-directed bending. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Guéron,et al.  Evidence from base-pair kinetics for two types of adenine tract structures in solution: their relation to DNA curvature. , 1988, Biochemistry.

[8]  R L Jernigan,et al.  Influence of fluctuations on DNA curvature. A comparison of flexible and static wedge models of intrinsically bent DNA. , 1993, Journal of molecular biology.

[9]  R. H. Ritchie,et al.  Dielectric effects in biopolymers: The theory of ionic saturation revisited , 1985 .

[10]  R L Jernigan,et al.  Static and statistical bending of DNA evaluated by Monte Carlo simulations. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[11]  D M Crothers,et al.  Bent helical structure in kinetoplast DNA. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[12]  V. P. Chuprina.  Anomalous structure and properties of poly (dA).poly(dT). Computer simulation of the polynucleotide structure with the spine of hydration in the minor groove , 1987, Nucleic Acids Res..

[13]  R. Dickerson,et al.  Structure of the B-DNA decamer C-C-A-A-C-I-T-T-G-G in two different space groups: conformational flexibility of B-DNA. , 1993, Biochemistry.

[14]  T. Tullius,et al.  How the structure of an adenine tract depends on sequence context: a new model for the structure of TnAn DNA sequences. , 1993, Biochemistry.

[15]  D M Crothers,et al.  Intrinsically bent DNA. , 1990, The Journal of biological chemistry.

[16]  D. Goodsell,et al.  Bending and curvature calculations in B-DNA. , 1994, Nucleic acids research.

[17]  Hen-Ming Wu,et al.  DNA bending at adenine · thymine tracts , 1986, Nature.

[18]  A. Rich,et al.  A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[19]  I D Kuntz,et al.  Molecular dynamics simulations of small peptides: Dependence on dielectric model and pH , 1991, Biopolymers.

[20]  H R Drew,et al.  Reversible bending and helix geometry in a B-DNA dodecamer: CGCGAATTBrCGCG. , 1982, The Journal of biological chemistry.

[21]  C R Calladine,et al.  Mechanics of sequence-dependent stacking of bases in B-DNA. , 1982, Journal of molecular biology.

[22]  R. Lavery,et al.  Defining the structure of irregular nucleic acids: conventions and principles. , 1989, Journal of biomolecular structure & dynamics.

[23]  Y. Kyōgoku,et al.  One- and two-dimensional NMR studies on the conformation of DNA containing the oligo(dA)oligo(dT) tract. , 1988, Nucleic acids research.

[24]  W. Bauer,et al.  Calculation of the twist and the writhe for representative models of DNA. , 1986, Journal of molecular biology.

[25]  R Lavery,et al.  A general approach to the optimization of the conformation of ring molecules with an application to valinomycin. , 1986, Journal of biomolecular structure & dynamics.

[26]  R Lavery,et al.  Conformational sub-states in B-DNA. , 1992, Journal of molecular biology.

[27]  K. Breslauer,et al.  A spectroscopic and calorimetric study of the melting behaviors of a "bent" and a "normal" DNA duplex: [d(GA4T4C)]2 versus [d(GT4A4C)]2. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Crothers,et al.  A computer graphics study of sequence-directed bending in DNA. , 1983, Journal of biomolecular structure & dynamics.

[29]  R. Lavery,et al.  The flexibility of the nucleic acids: (II). The calculation of internal energy and applications to mononucleotide repeat DNA. , 1986, Journal of biomolecular structure & dynamics.

[30]  S. Harvey,et al.  Dehydrating agents sharply reduce curvature in DNAs containing A tracts. , 1995, Nucleic acids research.

[31]  P. V. von Hippel,et al.  DNA-protein interactions. , 1972, Annual review of biochemistry.

[32]  E. Trifonov,et al.  The pitch of chromatin DNA is reflected in its nucleotide sequence. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[33]  V. P. Chuprina,et al.  New insights into the structure of An tracts and B'-B' bends in DNA. , 1991, Biochemistry.

[34]  G. Otting,et al.  Hydration of DNA in aqueous solution: NMR evidence for a kinetic destabilization of the minor groove hydration of d-(TTAA)2 versus d-(AATT)2 segments. , 1994, Nucleic Acids Research.

[35]  Heinz Sklenar,et al.  JUMNA (junction minimisation of nucleic acids) , 1995 .

[36]  Thomas D. Tullius,et al.  Structural details of an adenine tract that does not cause DNA to bend , 1988, Nature.

[37]  S C Harvey,et al.  What is the basis of sequence-directed curvature in DNAs containing A tracts? , 1995, Journal of biomolecular structure & dynamics.

[38]  V. Zhurkin,et al.  Anisotropic flexibility of DNA and the nucleosomal structure. , 1979, Nucleic acids research.

[39]  D. Goodsell,et al.  "...the tyranny of the lattice...". , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[40]  R. Harrington.  DNA curving and bending in protein–DNA recognition , 1992, Molecular microbiology.