Barnaba: Software for Analysis of Nucleic Acids Structures and Trajectories

Bottaro, Sandro; Bussi, Giovanni; Pinamonti, Giovanni; Reißer, Sabine; Boomsma, Wouter; Lindorff‐Larsen, Kresten

doi:10.1101/345678

Cited by 3 publications

(3 citation statements)

References 53 publications

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“…The obtained weights were also validated using a WHAM procedure (see the SI). Figure 4 reports the dynamic secondary structure 48 for selected ensembles for both tetraloops as obtained using all the employed force fields, together with their native structures. When the ensemble is selected to only contain conformations where both the stem and the loop are formed, the dynamic secondary structure is highly homogeneous and, by construction, consistent with native.…”

mentioning

confidence: 99%

“…By only correcting dihedrals we were not able to obtain a force field capable of folding the investigated loops to the native structure with a significant population. However, 48 For all the other columns, we show dynamic secondary structure representations obtained with different force fields as indicated in the column name. The color scheme shows the fraction of frames for which the interaction is formed.…”

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confidence: 99%

“…Both three-dimensional and secondary structures are shown. Secondary structures were obtained with the BARNABA software 48. For all the other columns, we show dynamic secondary structure representations obtained with different force fields as indicated in the column name.…”

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confidence: 99%

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Fitting Corrections to an RNA Force Field Using Experimental Data

Cesari

Bottaro

Lindorff‐Larsen

et al. 2019

J. Chem. Theory Comput.

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116

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Empirical force fields for biomolecular systems are usually derived from quantum chemistry calculations and validated against experimental data. We here show how it is possible to refine the full dihedral-angle potential of the Amber RNA force field by using solution NMR data as well as stability of known structural motifs. The procedure can be used to mix multiple systems and heterogeneous experimental information and crucially depends on a regularization term chosen with a cross-validation procedure. By fitting corrections to the dihedral angles on the order of less than 1 kJ/mol per angle, it is possible to increase the stability of difficult-to-fold RNA tetraloops by more than 1 order of magnitude.

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confidence: 99%

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confidence: 99%

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Fitting Corrections to an RNA Force Field Using Experimental Data

Cesari

Bottaro

Lindorff‐Larsen

et al. 2019

J. Chem. Theory Comput.

Self Cite

116

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Mg²⁺Sensing by an RNA Fragment: Role of Mg²⁺Coordinated Water Molecules

Halder

Kumar

Valsson

et al. 2020

Preprint

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RNA molecules selectively bind to specific metal ions to populate their functional active states making it important to understand their source of ion selectivity. In large RNA systems, metal ions interact with the RNA at multiple locations making it difficult to decipher the precise role of ions in folding. To overcome this complexity, we studied the role of different metal ions (Mg 2+ , Ca 2+ and K + ) in the folding of a small RNA hairpin motif (5 -ucCAAAga-3 ) using unbiased all-atom molecular dynamics simulations. The advantage in studying this small system is that it requires specific binding of a single metal ion to fold to its native state. We find that even for this small RNA, the folding free energy surface (FES) is multidimensional as different metal ions present in the solution can simultaneously facilitate folding. The FES shows that specific binding of a metal ion is indispensable for its folding. We further show that in addition to the negatively charged phosphate groups, spatial organization of electronegative nucleobase atoms drive the site specific binding of the metal ion. Even though the binding site cannot discriminate between different metal ions, RNA folds efficiently only in Mg 2+ solution. We show that the rigid network of Mg 2+ coordinated water molecules facilitate the formation of important interactions in the transition state. The other metal ions such as K + and Ca 2+ cannot facilitate the formation of such interactions. These results allow us to hypothesize possible metal sensing mechanisms in large metallo-riboswitches and they also provide useful insights for the design of appropriate collective variables for studying large RNA molecules using enhanced sampling methods.

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Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting

Varricchio¹,

Mathez²,

Kaiser³

et al. 2022

Preprint

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SARS-CoV-2 is currently causing an unprecedented pandemic. While vaccines are massively deployed, we still lack effective large-scale antiviral therapies. In the quest for antivirals targeting conserved structures, we focused on molecules able to bind viral RNA secondary structures. Aminoglycosides are a class of antibiotics known to interact with the ribosomal RNA of both prokaryotes and eukaryotes and have previously been shown to exert antiviral activities by interacting with viral RNA. Here we show that the aminoglycoside geneticin is endowed with antiviral activity against all tested variants of SARS-CoV-2, in different cell lines and in a respiratory tissue model at non-toxic concentrations. The mechanism of action is an early inhibition of RNA replication and protein expression mediated by direct interaction with the −1 programmed ribosomal frameshift (PRF) signal. Using in silico modeling, we have identified a potential binding site of geneticin in the pseudoknot of frameshift RNA motif. Moreover, we have selected, through virtual screening, additional RNA binding compounds, interacting with the same site with increased potency.

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Barnaba: Software for Analysis of Nucleic Acids Structures and Trajectories

Abstract: RNA molecules are highly dynamic systems characterized by a 13 complex interplay between sequence, structure, dynamics, and function.

Cited by 3 publications

References 53 publications

Fitting Corrections to an RNA Force Field Using Experimental Data

Fitting Corrections to an RNA Force Field Using Experimental Data

Mg²⁺Sensing by an RNA Fragment: Role of Mg²⁺Coordinated Water Molecules

Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting

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Barnaba: Software for Analysis of Nucleic Acids Structures and Trajectories

Abstract: RNA molecules are highly dynamic systems characterized by a 13 complex interplay between sequence, structure, dynamics, and function.

Cited by 3 publications

References 53 publications

Fitting Corrections to an RNA Force Field Using Experimental Data

Fitting Corrections to an RNA Force Field Using Experimental Data

Mg2+Sensing by an RNA Fragment: Role of Mg2+Coordinated Water Molecules

Geneticin shows selective antiviral activity against SARS-CoV-2 by interfering with programmed -1 ribosomal frameshifting

Contact Info

Product

Resources

About

Mg²⁺Sensing by an RNA Fragment: Role of Mg²⁺Coordinated Water Molecules