Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate-DNA Helices Export

@article{citeulike:3097416, abstract = {Abstract: We apply continuum solvent models to investigate the relative stability of A- and B-form helices for three DNA sequences, d(CCAACGTTGG)2, d(ACCCGCGGGT)2, and d(CGCGAATTCGCG)2, a phosphoramidate-modified DNA duplex, p(CGCGAATTCGCG)2, in which the O3' atom in deoxyribose is replaced with NH, and an RNA duplex, r(CCAACGUUGG)2. Structures were taken as snapshots from multi-nanosecond molecular dynamics simulations computed in a consistent fashion using explicit solvent and with long-range electrostatics accounted for using the particle-mesh Ewald procedure. The electrostatic contribution to solvation energies were computed using both a finite-difference Poisson-Boltzmann (PB) model and a pairwise generalized Born model; nonelectrostatic contributions were estimated with a surface-area-dependent term. To these solvation free energies were added the mean solute internal energies (determined from a molecular mechanics potential) and estimates of the solute entropy (from a harmonic analysis). Consistent with experiment, the relative energies favor B-form helices for DNA and A-form helices for the NP-modified system and for RNA. Salt effects, modeled at the linear or nonlinear PB level, favor the A-form helices by modest amounts; for d(ACCCGCGGGT)2, salt is nearly able to switch the conformational preference to "A". The results provide a physical interpretation for the origins of the relative stabilities of A- and B-helices and suggest that similar analyses might be useful in a variety of nucleic acid conformational problems.}, address = {Contribution from the Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, Division of Computer Research and Technology, National Institutes of Health, Bethesda, Maryland 20892, Department of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland, and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143}, author = {Srinivasan, J. and Cheatham, T. E. and Cieplak, P. and Kollman, P. A. and Case, D. A.}, citeulike-article-id = {3097416}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja981844+}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja981844+}, day = {23}, doi = {10.1021/ja981844+}, journal = {J. Am. Chem. Soc.}, keywords = {dna\_ab}, month = {September}, number = {37}, pages = {9401--9409}, posted-at = {2008-08-08 05:53:34}, priority = {5}, title = {Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate-DNA Helices}, url = {http://dx.doi.org/10.1021/ja981844+}, volume = {120}, year = {1998} }

TY - JOUR ID - citeulike:3097416 L3 - citeulike-article-id:3097416 N2 - Abstract: We apply continuum solvent models to investigate the relative stability of A- and B-form helices for three DNA sequences, d(CCAACGTTGG)2, d(ACCCGCGGGT)2, and d(CGCGAATTCGCG)2, a phosphoramidate-modified DNA duplex, p(CGCGAATTCGCG)2, in which the O3' atom in deoxyribose is replaced with NH, and an RNA duplex, r(CCAACGUUGG)2. Structures were taken as snapshots from multi-nanosecond molecular dynamics simulations computed in a consistent fashion using explicit solvent and with long-range electrostatics accounted for using the particle-mesh Ewald procedure. The electrostatic contribution to solvation energies were computed using both a finite-difference Poisson-Boltzmann (PB) model and a pairwise generalized Born model; nonelectrostatic contributions were estimated with a surface-area-dependent term. To these solvation free energies were added the mean solute internal energies (determined from a molecular mechanics potential) and estimates of the solute entropy (from a harmonic analysis). Consistent with experiment, the relative energies favor B-form helices for DNA and A-form helices for the NP-modified system and for RNA. Salt effects, modeled at the linear or nonlinear PB level, favor the A-form helices by modest amounts; for d(ACCCGCGGGT)2, salt is nearly able to switch the conformational preference to "A". The results provide a physical interpretation for the origins of the relative stabilities of A- and B-helices and suggest that similar analyses might be useful in a variety of nucleic acid conformational problems. IS - 37 JF - J. Am. Chem. Soc. AD - Contribution from the Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, Division of Computer Research and Technology, National Institutes of Health, Bethesda, Maryland 20892, Department of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland, and Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94143 EP - 9409 TI - Continuum Solvent Studies of the Stability of DNA, RNA, and Phosphoramidate-DNA Helices VL - 120 SP - 9401 KW - dna_ab AU - Srinivasan, J AU - Cheatham, TE AU - Cieplak, P AU - Kollman, PA AU - Case, DA PY - 1998/09/23/ UR - http://dx.doi.org/10.1021/ja981844+ ER -