Already two water molecules change planar H-bonded structures of the adenine···thymine base pair to the stacked ones: a molecular dynamics simulations study

Kabeláč, Martin; Ryjáček, Filip; Hobza, Pavel

doi:10.1039/b007167f

Cited by 41 publications

(24 citation statements)

References 14 publications

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“…Thus the population of stacked arrangements is much larger than that of planar H‐bonded structures. This is comparable to what has been found already with two waters for the adeninethymine base pairs 30.…”

Section: Resultssupporting

confidence: 91%

5‐fluorouracil dimers in aqueous solution: molecular dynamics in water and continuum solvation*

Alagona¹,

Ghio²,

Monti³

2002

Int J of Quantum Chemistry

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ABSTRACT:The interactions established in aqueous solution by a variety of 5-fluorouracil (FU) dimers in water were examined to elucidate the strength of drug-solvent interactions. Molecular dynamics simulations for clusters made up of the FU dimer alone or embedded in 4, 12, and 100 waters at high temperature, followed by simulated annealing, allowed comparing the dimer structures in the different environments, the solute-solvent radial distribution functions and the cluster energetics. The statistics were consistent with those obtained from a 10 ns MD simulation in the NPT ensemble in 385 waters. Interestingly, the F atom was never preferred to O as H-bond acceptor either in the dimer or in water. The interactions within the dimers turned out to be remarkably affected by the presence of the solvent: stacked structures, unfavorable in the gas phase, prevailed even in the presence of four water molecules. The presence of real water molecules is thus of paramount importance to stabilize the system, using molecular dynamics or, alternatively, if affordable, the MP2 level. Geometry optimizations of the clusters at the B3LYP/6-31G * or HF/6-31G * level, in fact, though starting from a stacked hydrated arrangement of the FU dimer, produced almost exactly the same seashell structure. The polarizable continuum model is convenient to compute the solvation free energy of the dimers and clusters at the HF or MP2 level. Also, the partial charge distribution of the clusters can profitably be used to evaluate the solvent effect in the continuum framework.

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Section: Resultssupporting

confidence: 91%

5‐fluorouracil dimers in aqueous solution: molecular dynamics in water and continuum solvation*

Alagona¹,

Ghio²,

Monti³

2002

Int J of Quantum Chemistry

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“…Using empirical electrostatic potential, Hartree–Fock optimisation and MP2 single‐point calculations, the authors have shown that stacked dimers in the presence of two or three water molecules were slightly (by about 5 %) more stable than H‐bonded pairs. In our previous communication13 we showed that a gradual increase in the hydration number of the adenine ⋅⋅⋅ thymine NA base pair results in a transition from planar base‐pair structures to nonplanar ones and that, for as few as two water molecules, the population of stacked structures is higher than that of planar structures. Since we studied the interaction of free bases, both orientations of bases in the stacked arrangement (face to face or face to back) are possible.…”

Section: Introductionmentioning

confidence: 98%

At Nonzero Temperatures, Stacked Structures of Methylated Nucleic Acid Base Pairs and Microhydrated Nonmethylated Nucleic Acid Base Pairs are Favored over Planar Hydrogen-Bonded Structures: A Molecular Dynamics Simulations Study

Kabeláč

Hobza

2001

Chem. Eur. J.

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The dynamic structure of all ten possible nucleic acid (NA) base pairs and methylated NA base pairs hydrated by a small number of water molecules (from 1 to 16) was determined by using molecular dynamics simulations in the NVE microcanonical and NVT canonical ensembles with the Cornell force field (W. D. Cornell, P. Cieplak, C. I. Bayly, I. R. Gould, K. M. Merz, D. M. Ferguson, D. C. Spellmeyer, T. Fox, J. E. Caldwell, P. Kollman, J. Am. Chem. Soc. 1995, 117, 5179). The presence of one water molecule does not affect the structure of any hydrogen-bonded (H-bonded) nonmethylated base pair. An equal population of H-bonded and stacked structures of adenine...adenine, adenine...guanine and adenine... thymine pairs is reached if as few as two water molecules are present, while obtaining equal populations of these structures in the case of adenine...cytosine, cytosine...thymine, guanine... guanine and guanine...thymine required the presence of four water molecules, and in the case of guanine...cytosine, six. A comparable population of planar, H-bonded and stacked structures for cytosine...cytosine and thymine... thymine base pairs was only obtained if at least eight water molecules hydrated a pair. Methylation of bases changed the situation dramatically and stacked structures were favoured over H-bonded ones even in the absence of water molecules in most cases. Only in the case of methyl cytosine...methyl cytosine, methyl guanine...methyl guanine and methyl guanine...methyl cytosine pairs were two, two or six water molecules, respectively, needed in order to obtain a comparable population of planar, H-bonded and stacked structures. We believe that these results give clear evidence that the preferred stacked structure of NA base pairs in the microhydrated environment, and also apparently in a regular solvent, is due to the hydrophilic interaction of a small number of water molecules. In the case of methylated bases, it is also due to the fact that the hydrogen atoms most suitable for the formation of H-bonds have been replaced by a methyl group. A preferred stacked structure is, thus, not due to a hydrophobic interaction between a large bulk of water molecules and the base pair, as believed.

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“…In the heavily hydrated conditions, the geometrical structures of nucleic acid bases have been revealed to be significantly deformed15, 16. Further, hydration has been found to increase the stability of some minor tautomers of nucleic acid bases17, 18 as well as the stacking interactions in base pairs19–21. Based upon the crystallographic study of hydrated DNA bases, Schneider et al22 have shown that degree of hydration generally depends upon different factors, such as the DNA type, nucleic acid bases, and locations of minor and major groves sites.…”

Section: Introductionmentioning

confidence: 99%

Guanine in water solution: Comprehensive study of hydration cage versus continuum solvation model

Shukla

Leszczyński

2010

Int J of Quantum Chemistry

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ABSTRACT:We report the results of computational investigation of structures and properties of deoxyribonucleic acid base guanine in the isolated and under heavily hydrated conditions. Heavily hydrated condition involves guanine inside the hydrated cage of 65 water molecules. For comparison, results of hydration of guanine with smaller water shells and that in bulk water solution are also presented. Ground state geometries were optimized at the Hartree-Fock and density functional theory (DFT) level using the B3LYP functional. Vertical electronic singlet transitions were computed at the time-dependent DFT level using the B3LYP optimized geometries. Geometries in the electronic lowest singlet pp* excited state were optimized at the CIS level of the theory. Effect of bulk water solution was considered using the PCM approach. The standard 6-311G(d,p) basis set was used in all calculations. The similarity and differences between these two models (bulk water solvation and hydration) in describing the aqueous environment on guanine are also reported. It has been found that hydration with 65 water molecule and PCM solvation both produce similar ground and excited state geometry of guanine. In addition, the possible effect of selective hydration on the excited state dynamics is also discussed.

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Already two water molecules change planar H-bonded structures of the adenine···thymine base pair to the stacked ones: a molecular dynamics simulations study

Cited by 41 publications

References 14 publications

5‐fluorouracil dimers in aqueous solution: molecular dynamics in water and continuum solvation*

5‐fluorouracil dimers in aqueous solution: molecular dynamics in water and continuum solvation*

At Nonzero Temperatures, Stacked Structures of Methylated Nucleic Acid Base Pairs and Microhydrated Nonmethylated Nucleic Acid Base Pairs are Favored over Planar Hydrogen-Bonded Structures: A Molecular Dynamics Simulations Study

Guanine in water solution: Comprehensive study of hydration cage versus continuum solvation model

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