Structural bioinformatics of DNA: a web-based tool for the analysis of molecular dynamics results and structure prediction

UNLABELLED We report here the release of a web-based tool (MDDNA) to study and model the fine structural details of DNA on the basis of data extracted from a set of molecular dynamics (MD) trajectories of DNA sequences involving all the unique tetranucleotides. The dynamic web interface can be employed to analyze the first neighbor sequence context effects on the 10 unique dinucleotide steps of DNA. Functionality is included to build all atom models of any user-defined sequence based on the MD results. The backend of this interface is a relational database storing the conformational details of DNA obtained in 39 different MD simulation trajectories comprising all the 136 unique tetranucleotide steps. Examples of the use of this data to predict DNA structures are included. AVAILABILITY http://humphry.chem.wesleyan.edu:8080/MDDNA. SUPPLEMENTARY INFORMATION Supplementary data including color figures are available at Bioinformatics online.

[1]  H M Berman,et al.  A standard reference frame for the description of nucleic acid base-pair geometry. , 2001, Journal of molecular biology.

[2]  H M Berman,et al.  Nucleic acid crystallography: a view from the nucleic acid database. , 1996, Progress in biophysics and molecular biology.

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

[4]  Lennart Nilsson,et al.  Molecular dynamics applied to nucleic acids. , 2002, Accounts of chemical research.

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

[6]  Richard E. Dickerson,et al.  The DNA Helix and How it is Read , 1983 .

[7]  S. Neidle.  Oxford handbook of nucleic acid structure , 1998 .

[8]  S. Diekmann,et al.  Definitions and nomenclature of nucleic acid structure parameters. , 1989, Journal of molecular biology.

[9]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules J. Am. Chem. Soc. 1995, 117, 5179−5197 , 1996 .

[10]  Heinz Sklenar,et al.  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. , 2005, Biophysical journal.

[11]  Thomas E Cheatham,et al.  Simulation and modeling of nucleic acid structure, dynamics and interactions. , 2004, Current opinion in structural biology.

[12]  P. Lu,et al.  Residual dipolar couplings in nucleic acid structure determination. , 2002, Current opinion in structural biology.

[13]  Kelly M. Thayer,et al.  Molecular dynamics simulations of DNA curvature and flexibility: Helix phasing and premelting , 2004, Biopolymers.

[14]  F. J. Luque,et al.  Theoretical methods for the simulation of nucleic acids. , 2003, Chemical Society reviews.

[15]  Richard Lavery,et al.  Simulations of nucleic acids and their complexes. , 2002, Accounts of chemical research.

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

[17]  I. Brukner,et al.  Differential behavior of curved DNA upon untwisting. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P Shing Ho,et al.  How sequence defines structure: a crystallographic map of DNA structure and conformation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Alexander D. MacKerell.  Empirical force fields for biological macromolecules: Overview and issues , 2004, J. Comput. Chem..

[20]  Heinz Sklenar,et al.  Molecular dynamics simulations of the 136 unique tetranucleotide sequences of DNA oligonucleotides. I. Research design and results on d(CpG) steps. , 2004, Biophysical journal.

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

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

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

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

[25]  Martin J Packer,et al.  Prediction of atomic structure from sequence for double helical DNA oligomers , 2006, Biopolymers.