Ions in Molecular Dynamics Simulations of RNA Systems

Auffinger, Pascal

doi:10.1007/978-3-642-25740-7_14

Cited by 9 publications

(5 citation statements)

References 98 publications

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“…MD simulations have been used extensively to study monovalent cation interactions with nucleic acids ( 35 – 37 , 84 , 87 – 100 ) driven in part by development of new force fields ( 37 , 78 , 80 , 90 , 93 ). These studies have provided insight at atomic level into the role of competitive binding of ions to phosphoryl groups ( 91 , 92 ) and the grooves ( 87 – 88 , 98 , 101 , 102 ).…”

Section: Resultsmentioning

confidence: 99%

Competitive interaction of monovalent cations with DNA from 3D-RISM

et al. 2015

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The composition of the ion atmosphere surrounding nucleic acids affects their folding, condensation and binding to other molecules. It is thus of fundamental importance to gain predictive insight into the formation of the ion atmosphere and thermodynamic consequences when varying ionic conditions. An early step toward this goal is to benchmark computational models against quantitative experimental measurements. Herein, we test the ability of the three dimensional reference interaction site model (3D-RISM) to reproduce preferential interaction parameters determined from ion counting (IC) experiments for mixed alkali chlorides and dsDNA. Calculations agree well with experiment with slight deviations for salt concentrations >200 mM and capture the observed trend where the extent of cation accumulation around the DNA varies inversely with its ionic size. Ion distributions indicate that the smaller, more competitive cations accumulate to a greater extent near the phosphoryl groups, penetrating deeper into the grooves. In accord with experiment, calculated IC profiles do not vary with sequence, although the predicted ion distributions in the grooves are sequence and ion size dependent. Calculations on other nucleic acid conformations predict that the variation in linear charge density has a minor effect on the extent of cation competition.

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Section: Resultsmentioning

confidence: 99%

Competitive interaction of monovalent cations with DNA from 3D-RISM

et al. 2015

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“…Divalent cations were not included due to the known artifacts in simulations. [69] The A-site models in the context of 70S ribosome were built based on crystal structures 3TVF(30S)/3TVE(50S) (cognate) and 3UYD(30S)/3UYE(50S) (near-cognate), respectively. [26] The ribosomal residues within a radius of 25 Å from the center of A1492/3 nucleobases were included to model the ribosomal A-site.…”

Section: Methodsmentioning

confidence: 99%

Flipping of the Ribosomal A-Site Adenines Provides a Basis for tRNA Selection

Zhang

Chugh

Casiano-Negroni

et al. 2014

Journal of Molecular Biology

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Ribosomes control the missense error rate of ~10−4 during translation though quantitative contributions of individual mechanistic steps of the conformational changes yet to be fully determined. Biochemical and biophysical studies led to a qualitative tRNA selection model in which ribosomal A-site residues A1492 and A1493 (A1492/3) flip out in response to cognate tRNA binding, promoting the subsequent reactions, but not in the case of near cognate or non-cognate tRNA. However, this model was recently questioned by X-ray structures revealing conformations of extrahelical A1492/3 and domain closure of the decoding center in both cognate and near-cognate tRNA bound ribosome complexes, suggesting that the non-specific flipping of A1492/3 has no active role in tRNA selection. We explore this question by carrying out molecular dynamics (MD) simulations, aided with fluorescence and NMR experiments, to probe the free energy cost of extrahelical flipping of 1492/3 and the strain energy associated with domain conformational change. Our rigorous calculations demonstrate that the A1492/3 flipping is indeed a specific response to the binding of cognate tRNA, contributing 3 kcal/mol to the specificity of tRNA selection. Furthermore, the different A-minor interactions in cognate and near-cognate complexes propagate into the conformational strain and contribute another 4 kcal/mol in domain closure. The recent structure of ribosome with features of extrahelical A1492/3 and closed domain in near-cognate complex is reconciled by possible tautomerization of the wobble base pair in mRNA-tRNA. These results quantitatively rationalize other independent experimental observations and explain the ribosomal discrimination mechanism of selecting cognate versus near-cognate tRNA.

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“…Therefore, their structural and dynamical features may be affected by ionic conditions. − Noncanonical quadruplex DNA and folded RNA molecules formed by complex hierarchy of molecular building blocks − are even more sensitive to ionic conditions than the duplexes. − Various aspects of ion binding to nucleic acids and effects of ion binding on nucleic acid structure have been studied by diverse experimental techniques. ,,,− However, as extensively discussed in the literature, ,,− experimental techniques to study ion binding to nucleic acids face some limitations, and thus the present knowledge of cation–nucleic acid interactions is far from being complete. In this respect, atomistic molecular dynamics (MD) simulations may provide useful complementary information to the results of experimental techniques. − In general, MD simulations are able to deliver valuable data about structural dynamics of nucleic acids. − Contemporary simulations are obviously based on many approximations, which limit their predictive power in studies of structural dynamics of nucleic acids and ion binding to nucleic acids. Besides the substantial force field approximations (use of simple nonpolarizable effective pair additive potentials), there are some others, such as the finite (and rather small) size of simulation boxes, particle mesh Ewald technique accounting for electrostatic interactions under used periodic boundary conditions, and so forth. ,, These approximations may complicate straightforward comparison of experimental and simulation salt conditions. ,,…”

Section: Introductionmentioning

confidence: 99%

Simulations of A-RNA Duplexes. The Effect of Sequence, Solute Force Field, Water Model, and Salt Concentration

et al. 2012

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We have carried out an extended reference set of explicit solvent molecular dynamics simulations (63 simulations with 8.4 μs of simulation data) of canonical A-RNA duplexes. Most of the simulations were done using the latest variant of the Cornell et al. AMBER RNA force field bsc0χ(OL3), while several other RNA force fields have been tested. The calculations show that the A-RNA helix compactness, described mainly by geometrical parameters inclination, base pair roll, and helical rise, is sequence-dependent. In the calculated set of structures, the inclination varies from 10° to 24°. On the basis of simulations with modified bases (inosine and 2,6-diaminopurine), we suggest that the sequence-dependence of purely canonical A-RNA double helix is caused by the steric shape of the base pairs, i.e., the van der Waals interactions. The electrostatic part of stacking does not appear to affect the A-RNA shape. Especially visible is the role of the minor groove amino group of purines. This resembles the so-called Dickerson-Calladine mechanical rules suggested three decades ago for the DNA double helices. We did not identify any long-living backbone substate in A-RNA double helices that would resemble, for example, the B-DNA BI/BII dynamics. The variability of the A-RNA compactness is due to mutual movements of the consecutive base pairs coupled with modest change of the glycosidic χ torsion. The simulations further show that the A-RNA compactness is modestly affected by the water model used, while the effect of ionic conditions, investigated in the range from net-neutral condition to ~0.8 M monovalent ion excess salt, is smaller.

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Ions in Molecular Dynamics Simulations of RNA Systems

Cited by 9 publications

References 98 publications

Competitive interaction of monovalent cations with DNA from 3D-RISM

Competitive interaction of monovalent cations with DNA from 3D-RISM

Flipping of the Ribosomal A-Site Adenines Provides a Basis for tRNA Selection

Simulations of A-RNA Duplexes. The Effect of Sequence, Solute Force Field, Water Model, and Salt Concentration

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