Structural equilibrium of DNA represented with different force fields.

We have recently indicated preliminary evidence of different equilibrium average structures with the CHARMM and AMBER force fields in explicit solvent molecular dynamics simulations on the DNA duplex d(C5T5) . d(A5G5) (Feig, M. and B.M. Pettitt, 1997, Experiment vs. Force Fields: DNA conformation from molecular dynamics simulations. J. Phys. Chem. B. (101:7361-7363). This paper presents a detailed comparison of DNA structure and dynamics for both force fields from extended simulation times of 10 ns each. Average structures display an A-DNA base geometry with the CHARMM force field and a base geometry that is intermediate between A- and B-DNA with the AMBER force field. The backbone assumes B form on both strands with the AMBER force field, while the CHARMM force field produces heterogeneous structures with the purine strand in A form and the pyrimidine strand in dynamical equilibrium between A and B conformations. The results compare well with experimental data for the cytosine/guanine part but fail to fully reproduce an overall B conformation in the thymine/adenine tract expected from crystallographic data, particularly with the CHARMM force field. Fluctuations between A and B conformations are observed on the nanosecond time scale in both simulations, particularly with the AMBER force field. Different dynamical behavior during the first 4 ns indicates that convergence times of several nanoseconds are necessary to fully establish a dynamical equilibrium in all structural quantities on the time scale of the simulations presented here.

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

[2]  U. Heinemann,et al.  Crystallographic study of one turn of G/C-rich B-DNA. , 1989, Journal of molecular biology.

[3]  A. Rich,et al.  The crystal structure of d(CCCCGGGG): a new A-form variant with an extended backbone conformation. , 1987, Journal of biomolecular structure & dynamics.

[4]  P A Kollman,et al.  Observation of the A-DNA to B-DNA transition during unrestrained molecular dynamics in aqueous solution. , 1996, Journal of molecular biology.

[5]  U Heinemann,et al.  Helix geometry, hydration, and G.A mismatch in a B-DNA decamer. , 1987, Science.

[6]  H R Drew,et al.  The intrinsic curvature of DNA in solution. , 1988, Journal of molecular biology.

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

[8]  R. Keyes,et al.  Overall and internal dynamics of DNA as monitored by five-atom-tethered spin labels. , 1997, Biophysical journal.

[9]  P. Hagerman.  Straightening out the bends in curved DNA. , 1992, Biochimica et biophysica acta.

[10]  B. Boettcher.  Transcription initiation and nuclease-sensitive sites upstream of the epsilon-globin gene in K562 cells are related to poly (dA).poly (dT) sequences. , 1990, Journal of theoretical biology.

[11]  T. Steitz,et al.  A DNA dodecamer containing an adenine tract crystallizes in a unique lattice and exhibits a new bend. , 1993, Journal of molecular biology.

[12]  A. Sarvazyan,et al.  Acoustical investigation of poly(dA).poly(dT), poly[d(A-T)].poly[d(A-T)], poly(A) . poly(U) and DNA hydration in dilute aqueous solutions , 1989 .

[13]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[14]  P. Kollman,et al.  Molecular Dynamics Simulations on Solvated Biomolecular Systems: The Particle Mesh Ewald Method Leads to Stable Trajectories of DNA, RNA, and Proteins , 1995 .

[15]  D S Goodsell,et al.  The effect of crystal packing on oligonucleotide double helix structure. , 1987, Journal of biomolecular structure & dynamics.

[16]  R. Dickerson,et al.  Analysis of local helix geometry in three B-DNA decamers and eight dodecamers. , 1991, Journal of molecular biology.

[17]  A. Lane.  Determination of fast dynamics of nucleic acids by NMR. , 1995, Methods in enzymology.

[18]  C R Calladine,et al.  The assessment of the geometry of dinucleotide steps in double-helical DNA; a new local calculation scheme. , 1995, Journal of molecular biology.

[19]  D. Kearns,et al.  Internal motions in B- and Z-form poly(dG-dC).poly(dG-dC): 1H NMR relaxation studies. , 1985, Biochemistry.

[20]  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.

[21]  R Lavery,et al.  BI-BII transitions in B-DNA. , 1993, Nucleic acids research.

[22]  R. Dickerson,et al.  The structure of B-helical C-G-A-T-C-G-A-T-C-G and comparison with C-C-A-A-C-G-T-T-G-G. The effect of base pair reversals. , 1991, The Journal of biological chemistry.

[23]  D. Goodsell,et al.  The crystal structure of C-C-A-T-T-A-A-T-G-G. Implications for bending of B-DNA at T-A steps. , 1994, Journal of molecular biology.

[24]  B. Ramakrishnan,et al.  Evidence for crystal environment dominating base sequence effects on DNA conformation: crystal structures of the orthorhombic and hexagonal polymorphs of the A-DNA decamer d(GCGGGCCCGC) and comparison with their isomorphous crystal structures. , 1993, Biochemistry.

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

[26]  W. Olson,et al.  The effect of mathematics and coordinate system on comparability and "dependencies" of nucleic acid structure parameters. , 1994, Journal of molecular biology.

[27]  B. Montgomery Pettitt,et al.  Efficient Ewald electrostatic calculations for large systems , 1995 .

[28]  Bernard R. Brooks,et al.  New spherical‐cutoff methods for long‐range forces in macromolecular simulation , 1994, J. Comput. Chem..

[29]  S. Diekmann,et al.  Definitions and nomenclature of nucleic acid structure parameters. , 1989, The EMBO journal.

[30]  H. Sklenar,et al.  NMR studies and restrained-molecular-dynamics calculations of a long A+T-rich stretch in DNA. Effects of phosphate charge and solvent approximations. , 1995, European journal of biochemistry.

[31]  S. Edmondson.  Polynucleotide base‐pair orientation in solution: Linear dichroism and molecular mechanical studies of poly[d(A)]‐poly[d(T)] , 1987, Biopolymers.

[32]  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.

[33]  O Kennard,et al.  The crystal structure of d(G-G-G-G-C-C-C-C). A model for poly(dG).poly(dC). , 1985, Journal of molecular biology.

[34]  S. Edmondson,et al.  Base tilt of B‐form poly[d(G)]‐poly[d(C)] and the B‐ and Z‐conformations of poly[d(GC)]‐poly[d(GC)] in solution , 1986, Biopolymers.

[35]  J M Rosenberg,et al.  Molecular dynamics simulation study of DNA dodecamer d(CGCGAATTCGCG) in solution: conformation and hydration. , 1997, Journal of molecular biology.

[36]  D. Kearns,et al.  1H two-dimensional nuclear Overhauser effect and relaxation studies of poly(dA).poly(dT) , 1986, Biochemistry.

[37]  E Westhof,et al.  Calculations of nucleic acid conformations. , 1996, Current opinion in structural biology.

[38]  H. Berman,et al.  Analysis of local helix bending in crystal structures of DNA oligonucleotides and DNA-protein complexes. , 1995, Biophysical journal.

[39]  S Neidle,et al.  Molecular structure of the B-DNA dodecamer d(CGCAAATTTGCG)2. An examination of propeller twist and minor-groove water structure at 2.2 A resolution. , 1992, Journal of molecular biology.

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

[41]  B. Pettitt,et al.  Experiment vs force fields: DNA conformation from molecular dynamics simulations , 1997 .

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

[43]  C. C. Hardin,et al.  Conformational analysis of d(C3G3), a B-family duplex in solution. , 1989, Biochemistry.

[44]  G. Schroth,et al.  Alternating and non-alternating dG-dC hexanucleotides crystallize as canonical A-DNA. , 1996, Journal of molecular biology.

[45]  W. Denny,et al.  Infrared and Raman studies show that poly(dA).poly(dT) and d(AAAAATTTTT)2 exhibit a heteronomous conformation in films at 75% relative humidity and a B-type conformation at high humidities and in solution. , 1987, Biochemistry.

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

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

[48]  Y. Nishimura,et al.  Salt induced B----A transition of poly(dG).poly(dC) and the stabilization of A form by its methylation. , 1986, Nucleic acids research.

[49]  P. Turpin,et al.  The poly dA strand of poly dA.poly dT adopts an A-form in solution: a UV resonance Raman study. , 1985, Nucleic acids research.

[50]  T. Darden,et al.  Accurate crystal molecular dynamics simulations using particle-mesh-Ewald: RNA dinucleotides — ApU and GpC , 1995 .

[51]  J. Brahms,et al.  DNA with adenine tracts contains poly(dA).poly(dT) conformational features in solution. , 1990, Nucleic acids research.

[52]  G. A. van der Marel,et al.  Conformational analysis of the octamer d(G-G-C-C-G-G-C-C) in aqueous solution. A one-dimensional and two-dimensional proton NMR study at 300 MHz and 500 MHz. , 1986, European journal of biochemistry.

[53]  D. Beveridge,et al.  A 5-nanosecond molecular dynamics trajectory for B-DNA: analysis of structure, motions, and solvation. , 1997, Biophysical journal.

[54]  J. Mccammon,et al.  Dynamics of Proteins and Nucleic Acids , 2018 .

[55]  H R Drew,et al.  Principles of sequence-dependent flexure of DNA. , 1986, Journal of molecular biology.

[56]  C. Tung,et al.  Structural prediction of A- and B-DNA duplexes based on coordinates of the phosphorus atoms. , 1996, Biophysical journal.

[57]  A. Lipanov,et al.  Poly(dA)\ṁpoly(dT) is a B-type double helix with a distinctively narrow minor groove , 1987, Nature.

[58]  W. Peticolas,et al.  Effect of cross-linking on the secondary structure of DNA I. Cross-linking by photodimerization. , 1976, Biochemistry.

[59]  R. Dickerson,et al.  DNA structure from A to Z. , 1992, Methods in enzymology.

[60]  M. Searle,et al.  Sequence specific conformation of a DNA decamer containing an adenine tract studied in solution by H-NMR spectroscopy. , 1990, Biochimica et biophysica acta.

[61]  G. Ciccotti,et al.  Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes , 1977 .

[62]  R. Friedberg,et al.  Test of the Monte Carlo Method: Fast Simulation of a Small Ising Lattice , 1970 .

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

[64]  B. Montgomery Pettitt,et al.  MODELING SOLVENT IN BIOMOLECULAR SYSTEMS , 1994 .

[65]  R. Sarma,et al.  Untenability of the heteronomous DNA model for poly(dA).poly(dT) in solution. This DNA adopts a right-handed B-DNA duplex in which the two strands are conformationally equivalent. A 500 MHz NMR study using one dimensional NOE. , 1985, Journal of biomolecular structure & dynamics.

[66]  A. Sarvazyan,et al.  Influence of Drug Binding on DNA Hydration: Acoustic and Densimetric Characterizations of Netropsin Binding to the Poly(dAdT).cntdot.Poly(dAdT) and Poly(dA).cntdot.Poly(dT) Duplexes and the Poly(dT).cntdot.Poly(dA).cntdot.Poly(dT) Triplex at 25 .degree.C , 1994 .

[67]  K. Wüthrich,et al.  Conformational studies of d-(AAAAATTTTT)2 using constraints from nuclear overhauser effects and from quantitative analysis of the cross-peak fine structures in two-dimensional 1H nuclear magnetic resonance spectra. , 1989, Biochemistry.

[68]  E. Westhof,et al.  H-bond stability in the tRNA(Asp) anticodon hairpin: 3 ns of multiple molecular dynamics simulations. , 1996, Biophysical journal.

[69]  H. Schreiber,et al.  Molecular dynamics studies of solvated polypeptides: Why the cut-off scheme does not work , 1992 .

[70]  M. Sundaralingam,et al.  Effect of crystal packing environment on conformation of the DNA duplex. Molecular structure of the A-DNA octamer d(G-T-G-T-A-C-A-C) in two crystal forms. , 1989, The Journal of biological chemistry.

[71]  P. Kollman.  Advances and Continuing Challenges in Achieving Realistic and Predictive Simulations of the Properties of Organic and Biological Molecules , 1996 .

[72]  P. P. Ewald.  Die Berechnung optischer und elektrostatischer Gitterpotentiale , 1921 .

[73]  P. Kollman,et al.  Molecular Dynamics Simulations Find That 3‘ Phosphoramidate Modified DNA Duplexes Undergo a B to A Transition and Normal DNA Duplexes an A to B Transition , 1997 .

[74]  P. Auffinger,et al.  A simple test for evaluating the truncation effects in simulations of systems involving charged groups , 1995 .

[75]  L. Arnold,et al.  Comparison of the solution and crystal conformations of (G + C)-rich fragments of DNA. , 1996, Biophysical journal.

[76]  W. Peticolas,et al.  Fluctuations in nucleic acid conformations. 2. Raman spectroscopic evidence of varying ring pucker in A-T polynucleotides , 1983 .

[77]  G. Jacucci,et al.  Comparing the efficiency of Metropolis Monte Carlo and molecular-dynamics methods for configuration space sampling , 1984 .

[78]  B. Montgomery Pettitt,et al.  B to A Transition of DNA on the Nanosecond Time Scale , 1996 .

[79]  T. Steitz,et al.  Crystal lattice packing is important in determining the bend of a DNA dodecamer containing an adenine tract. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[80]  J. Banavar,et al.  Computer Simulation of Liquids , 1988 .

[81]  A. Palleschi,et al.  Validity of the nearest-neighbor approximation in the evaluation of the electrophoretic manifestations of DNA curvature. , 1990, Biochemistry.

[82]  Wolfram Saenger,et al.  Principles of Nucleic Acid Structure , 1983 .

[83]  S. A. Lee,et al.  The origin of the A to B transition in DNA fibers and films , 1988, Biopolymers.

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

[85]  E. Pednault,et al.  Nucleic acid structure analysis. Mathematics for local Cartesian and helical structure parameters that are truly comparable between structures. , 1994, Journal of molecular biology.

[86]  G. A. Thomas,et al.  A duplex of the oligonucleotides d(GGGGGTTTTT) and d(AAAAACCCCC) forms an A to B conformational junction in concentrated salt solutions. , 1989, Journal of biomolecular structure & dynamics.

[87]  A. Klug,et al.  The structure of an oligo(dA)·oligo(dT) tract and its biological implications , 1987, Nature.

[88]  J. Perram,et al.  Simulation of electrostatic systems in periodic boundary conditions. I. Lattice sums and dielectric constants , 1980, Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences.

[89]  V. Iyer,et al.  Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. , 1995, The EMBO journal.

[90]  J W Szostak,et al.  A poly(dA.dT) tract is a component of the recombination initiation site at the ARG4 locus in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[91]  V. Ivanov,et al.  The detection of B-form/A-form junction in a deoxyribonucleotide duplex. , 1996, Biophysical journal.

[92]  Bernard Pettitt,et al.  Peptides in ionic solutions: A comparison of the Ewald and switching function techniques , 1991 .

[93]  A. Rich,et al.  Raman spectra of single crystals of r(GCG)d(CGC) and d(CCCCGGGG) as models for A DNA, their structure transitions in aqueous solution, and comparison with double-helical poly(dG).poly(dC). , 1986, Biochemistry.

[94]  B. Montgomery Pettitt,et al.  Nanosecond Dynamics and Structure of a Model DNA Triple Helix in Saltwater Solution , 1995 .

[95]  R. Sarma,et al.  500-MHz 1H NMR study of poly(dG).poly(dC) in solution using one-dimensional nuclear Overhauser effect. , 1986, Biochemistry.

[96]  Bruno H. Zimm,et al.  Theory of twisting and bending of chain macromolecules; analysis of the fluorescence depolarization of DNA , 1979 .

[97]  H. Kang,et al.  Infrared linear dichroism reveals that A-, B-, and C-DNAs in films have bases highly inclined from perpendicular to the helix axis. , 1994, Biochemistry.

[98]  H M Berman,et al.  Conformations of the sugar-phosphate backbone in helical DNA crystal structures. , 1997, Biopolymers.

[99]  D. Rhodes,et al.  The DNA binding site of the Xenopus transcription factor IIIA has a non‐B‐form structure. , 1989, The EMBO journal.

[100]  D M Crothers,et al.  Sequence elements responsible for DNA curvature. , 1994, Journal of molecular biology.

[101]  R Lavery,et al.  The definition of generalized helicoidal parameters and of axis curvature for irregular nucleic acids. , 1988, Journal of biomolecular structure & dynamics.