Solution conformations of two naturally occurring RNA nucleosides: 3-Methyluridine and 3-methylpseudouridine

Desaulniers, Jean-Paul; Chui, Helen M P; Chow, Christine S.

doi:10.1016/j.bmc.2005.07.061

Cited by 16 publications

(19 citation statements)

References 53 publications

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“…Interestingly in nucleoside simulations Ψ mainly sampled the syn conformation (Fig. a), which agrees with experiments on nucleoside Ψ or its base‐alkyl derivatives, where Ψs were found in syn and their U counterparts in anti . No significant pucker preference of Ψs was seen in these experiments, nor in our simulations (Fig.…”

Section: Resultssupporting

confidence: 90%

Additive CHARMM force field for naturally occurring modified ribonucleotides

Vanommeslaeghe

Aleksandrov

et al. 2016

J Comput Chem

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More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of wide range of RNAs containing modified nucleotides including the ribosome and transfer RNAs.

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Section: Resultssupporting

confidence: 90%

Additive CHARMM force field for naturally occurring modified ribonucleotides

Vanommeslaeghe

Aleksandrov

et al. 2016

J Comput Chem

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“…Sugar methylation leads to a slight enhanced preference for the C 3′ - endo (north) sugar pucker; whereas, base methylation leads to a slight decreased preference for the C 3′ - endo conformation. These results show that the effect of modifications on nucleoside conformation are subtle, which is consistent with previous studies on methylated or alkylated uridine and pseudouridine monomers 38, 39. Nonetheless, the methylations may have significant effects on RNA conformation when present in certain sequences or structural motifs due to long-range tertiary contacts within the RNA.…”

Section: Discussionsupporting

confidence: 91%

Synthesis and solution conformation studies of the modified nucleoside N4,2′-O-dimethylcytidine (m4Cm) and its analogues

Mahto

Chow

2008

Bioorganic & Medicinal Chemistry

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The dimethylated ribosomal nucleoside m 4 Cm and its monomethylated analogues Cm and m 4 C were synthesized. The conformations (syn versus anti) of the three modified nucleosides and cytidine were determined by CD and 1D NOE difference spectroscopy. The ribose sugar puckers were determined by the use of proton coupling constants. The position of modification (e.g., O versus N methylation) was found to have an effect on the sugar pucker of cytidine.

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“…For each of the modified nucleosides under this study, experimental (NMR) studies reported preference for the syn conformation [55][56][57] . With the FF99 and FF99_bsc0 parameters, each of the modified residues preferentially adopted the anti conformation 26,58 .…”

Section: Glycosidic Torsion Angle (𝛘)mentioning

confidence: 92%

“…The fraction (in %) of syn base orientation in the equilibrium ensembles of Ψ, m 1 Ψ (1MP), m 3 Ψ (3MP), and Ψm (MRP) at 300 K. The values reported here are the averages (along with the standard deviations) calculated from three independent sets of 16 ns REMD simulations. The modified nucleosides Ψ, m 1 Ψ (1MP), m 3 Ψ (3MP), and Ψm (MRP) have been reported to prefer the syn conformation[55][56][57] .…”

mentioning

confidence: 99%

Data-informed reparameterization of modified RNA and the effect of explicit water models: Application to pseudouridine and derivatives

Dutta

Deb

Sarzyñska

et al. 2021

Preprint

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Pseudouridine is the most abundant post-transcriptional modification in RNA. We have previously shown that the FF99-derived parameters for pseudouridine and some of its naturally occurring derivatives in the AMBER distribution either alone or in combination with the revised 𝛄 torsion parameters (parmbsc0) failed to reproduce their conformational characteristics observed experimentally (Deb I, et al. J. Chem. Inf. Model. 2014, 54 (4):1129–1142; Deb I, et al. J. Comput. Chem., 2016, 37:1576−1588; Dutta N, et al. J. Chem. Inf. Model. 2020, 60 (10):4995–5002). However, the application of the recommended bsc0 correction did lead to an improvement in the description not only of the distribution in the 𝛄 torsional space but also of the sugar pucker distributions. In an earlier study, we examined the transferability of the revised glycosidic torsion parameters (𝛘IDRP) for Ψ to its derivatives. We noticed that although these parameters in combination with the AMBER FF99-derived parameters and the revised 𝛄 torsional parameters resulted in conformational properties of these residues that were in better agreement with experimental observations, the sugar pucker distributions were still not reproduced accurately. Here we report a new set of glycosidic torsional parameters (𝛘ND) based on glycosidic torsional profiles that correspond to known conformational propensities and a new set of partial atomic charges for pseudouridine, 1-methylpseudouridine, 3-methylpseudouridine and 2′-O-methylpseudouridine and studied their effect on the conformational distributions using REMD simulations at the individual nucleoside level. We have also studied the effect of the choice of water model on the conformational characteristics of these modified nucleosides. Our observations suggest that the current revised set of parameters and partial atomic charges describe the sugar pucker distributions for these residues more accurately and that the choice of a suitable water model is important for the accurate description of their conformational properties.

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Solution conformations of two naturally occurring RNA nucleosides: 3-Methyluridine and 3-methylpseudouridine

Cited by 16 publications

References 53 publications

Additive CHARMM force field for naturally occurring modified ribonucleotides

Additive CHARMM force field for naturally occurring modified ribonucleotides

Synthesis and solution conformation studies of the modified nucleoside N4,2′-O-dimethylcytidine (m4Cm) and its analogues

Data-informed reparameterization of modified RNA and the effect of explicit water models: Application to pseudouridine and derivatives

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