Intramolecular Base Stacking of Dinucleoside Monophosphate Anions in Aqueous Solution

Jafilan, Salem; Klein, Leah; Hyun, Christian; Florián, Jan

doi:10.1021/jp209986y

Cited by 47 publications

(74 citation statements)

References 44 publications

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“…In one respect this result is encouraging, but in another it is simply to be expected: force fields in general have developed considerably in the years since the Nilsson group’s seminal studies 12–16 were performed and a number of important updates 20a, 20e, 23 have since been made to the AMBER force field used in the Florian group’s studies. 19 Differences between our data and the Florian group’s data may also be at least partly due to the different temperatures at which the studies were conducted (298 versus 310 K respectively): the Nilsson group has previously shown that stacking PMFs can be sensitive to temperature, 15 an issue that has also been examined in detail by Chen & Garcia (see below). 41 We have not explored the effects of temperature here but we have attempted to gauge the potential impact of the most recent of the changes to the AMBER force field – i.e.…”

Section: Discussionmentioning

confidence: 56%

“…32 Finally, the Florian group proposed another very reasonable definition in which the distance between the centers of mass and the angle between the base planes were creatively combined to produce a single reaction coordinate. 19 Here, we use a similar but different approach to those used in these previous studies and define stacking using a combination of three criteria: (1) a minimum distance between any pair of heavy atoms in the two bases < 4 Å, (2) a distance between the center of mass of each base of < 5 Å, and (3) a vector angle between the normals to the planes of the two bases between 0 – 45° or between 135 – 180°. The first two of these properties were measured for each snapshot using the standard GROMACS utilities g_mindist and g_dist respectively, the third was measured using a script written in-house.…”

Section: Methodsmentioning

confidence: 99%

“…16 The Okamoto group reported similar PMF calculations 17 for all 16 DNA DNMPs using replica exchange techniques in combination with umbrella sampling; quite different results were obtained from those reported by the Nilsson group but these differences were suggested to be most likely due to the use of different parameter sets (force fields) in the simulations. 18 Finally and most recently, the Florian group reported a comprehensive equilibrium MD simulation study of the stacking free energies in all possible DNA and RNA DNMPs at 310 K; 19 the same paper also reported an extensive analysis of the orientational preferences of the bases in stacked conformations.…”

Section: Introductionmentioning

confidence: 99%

“…We use current iterations of the AMBER simulation force fields for both DNA and RNA – both of which have been significantly revised by a number of groups recently 20 – and employ simulation times that are many times longer than those used previously (1–3 μs vs. 40 ns 19 ). These simulations allow us to directly compare stacking thermodynamics observed in DNMPs – in which the bases are covalently linked to each other – to those observed in NS pairs – in which the bases are not covalently linked.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Stacking Free Energies of All DNA and RNA Nucleoside Pairs and Dinucleoside-Monophosphates Computed Using Recently Revised AMBER Parameters and Compared with Experiment

Brown

Andrews

Elcock

2015

J. Chem. Theory Comput.

126

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We report the results of a series of 1 μs-long explicit-solvent molecular dynamics (MD) simulations performed to compare the free energies of stacking (ΔGstack) of all possible combinations of DNA and RNA nucleoside (NS) pairs and dinucleoside-monophosphates (DNMPs). For both NS-pairs and DNMPs we show that the computed stacking free energies are in reasonable qualitative agreement with experimental measurements, and appear to provide the closest correspondence with experiment yet found among computational studies; in all cases, however, the computed stacking free energies are too favorable relative to experiment. Comparisons of NS-pair systems indicate that stacking interactions are very similar in RNA and DNA systems except when a thymine or uracil base is involved: the presence of a thymine base favors stacking by ~0.3 kcal/mol relative to a uracil base. One exception is found in the self-stacking of cytidines, which are found to be significantly more favorable for the DNA form; an analysis of the rotational orientations sampled during stacking events suggests that this is likely to be due to more favorable sugar-sugar interactions in stacked complexes of deoxycytidines. Comparisons of the DNMP systems indicate that stacking interactions are more favorable in RNA than in DNA except, again, when thymine or uracil bases are involved. Finally, additional simulations performed using a previous generation of the AMBER force field – in which the description of glycosidic bond rotations was less than optimal – produce computed stacking free energies that are in poorer agreement with experimental data. Overall, the simulations provide a comprehensive view of stacking thermodynamics in NS pairs and in DNMPs as predicted by a state-of-the-art MD force field.

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Section: Discussionmentioning

confidence: 56%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stacking Free Energies of All DNA and RNA Nucleoside Pairs and Dinucleoside-Monophosphates Computed Using Recently Revised AMBER Parameters and Compared with Experiment

Brown

Andrews

Elcock

2015

J. Chem. Theory Comput.

126

View full text Add to dashboard Cite

show abstract

“…In fact, a face-to-face dimer is predicted to be the global minimum energy structure for a uracil-uracil stack [60]. It is important to search for both face-to-back and face-toface stacks and careful selection of the base stacking coordinate may help achieve this goal [62].…”

Section: Base Stackingmentioning

confidence: 99%

Excited States in DNA Strands Investigated by Ultrafast Laser Spectroscopy

Chen

Zhang

Kohler

2014

Topics in Current Chemistry

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Ultrafast laser experiments on carefully selected DNA model compounds probe the effects of base stacking, base pairing, and structural disorder on excited electronic states formed by UV absorption in single and double DNA strands. Direct π-orbital overlap between two stacked bases in a dinucleotide or in a longer single strand creates new excited states that decay orders of magnitude more slowly than the generally subpicosecond excited states of monomeric bases. Half or more of all excited states in single strands decay in this manner. Ultrafast mid-IR transient absorption experiments reveal that the long-lived excited states in a number of model compounds are charge transfer states formed by interbase electron transfer, which subsequently decay by charge recombination. The lifetimes of the charge transfer states are surprisingly independent of how the stacked bases are oriented, but disruption of π-stacking, either by elevating temperature or by adding a denaturing co-solvent, completely eliminates this decay channel. Time-resolved emission measurements support the conclusion that these states are populated very rapidly from initial excitons. These experiments also reveal the existence of populations of emissive excited states that decay on the nanosecond time scale. The quantum yield of these states is very small for UVB/UVC excitation, but increases at UVA wavelengths. In double strands, hydrogen bonding between bases perturbs, but does not quench, the long-lived excited states. Kinetic isotope effects on the excited-state dynamics suggest that intrastrand electron transfer may couple to interstrand proton transfer. By revealing how structure and non-covalent interactions affect excited-state dynamics, on-going experimental and theoretical studies of excited states in DNA strands can advance understanding of fundamental photophysics in other nanoscale systems.

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Nature and magnitude of aromatic base stacking in DNA and RNA: Quantum chemistry, molecular mechanics, and experiment

et al. 2013

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Base stacking is a major interaction shaping up and stabilizing nucleic acids. During the last decades, base stacking has been extensively studied by experimental and theoretical methods. Advanced quantum-chemical calculations clarified that base stacking is a common interaction, which in the first approximation can be described as combination of the three most basic contributions to molecular interactions, namely, electrostatic interaction, London dispersion attraction and short-range repulsion. There is not any specific π-π energy term associated with the delocalized π electrons of the aromatic rings that cannot be described by the mentioned contributions. The base stacking can be rather reasonably approximated by simple molecular simulation methods based on well-calibrated common force fields although the force fields do not include nonadditivity of stacking, anisotropy of dispersion interactions, and some other effects. However, description of stacking association in condensed phase and understanding of the stacking role in biomolecules remain a difficult problem, as the net base stacking forces always act in a complex and context-specific environment. Moreover, the stacking forces are balanced with many other energy contributions. Differences in definition of stacking in experimental and theoretical studies are explained.

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Intramolecular Base Stacking of Dinucleoside Monophosphate Anions in Aqueous Solution

Cited by 47 publications

References 44 publications

Stacking Free Energies of All DNA and RNA Nucleoside Pairs and Dinucleoside-Monophosphates Computed Using Recently Revised AMBER Parameters and Compared with Experiment

Stacking Free Energies of All DNA and RNA Nucleoside Pairs and Dinucleoside-Monophosphates Computed Using Recently Revised AMBER Parameters and Compared with Experiment

Excited States in DNA Strands Investigated by Ultrafast Laser Spectroscopy

Nature and magnitude of aromatic base stacking in DNA and RNA: Quantum chemistry, molecular mechanics, and experiment

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