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197 results on '"Auffinger, Pascal"'

1. RNA Dynamics from Experimental and Computational Approaches

Author

Bussi, Giovanni, Bonomi, Massimiliano, Gkeka, Paraskevi, Sattler, Michael, Al-Hashimi, Hashim M., Auffinger, Pascal, Duca, Maria, Foricher, Yann, Incarnato, Danny, Jones, Alisha N., Kirmizialtin, Serdal, Krepl, Miroslav, Orozco, Modesto, Palermo, Giulia, Pasquali, Samuela, Salmon, Loïc, Schwalbe, Harald, Westhof, Eric, and Zacharias, Martin

Subjects
Quantitative Biology - Biomolecules, Physics - Biological Physics
Abstract

Ribonucleic acids (RNA) are unique in that they can store genetic information, replicate and perform catalysis. Importantly, RNA molecules are highly dynamic, and thus determining the ensemble of conformations that they populate is crucial not only to elucidate their biological functions, but also for their potential use as therapeutic targets. Computational and experimental techniques provide complementary views on RNA dynamics, and their integration is fundamental to improve the accuracy of computations and the resolution of experiments. Recent exciting developments in this field, were discussed at the CECAM workshop ``RNA dynamics from experimental and computational approaches'', in Paris, June 26-28, 2023. This report outlines key `take-home' messages that emerged during this workshop from the presentations and discussions.

Published
2024
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5. Evidence for a hydroxide ion bridging two magnesium ions at the active site of the hammerhead ribozyme

Author

Hermann, Thomas, Auffinger, Pascal, Scott, William G, and Westhof, Eric

Subjects
Chemical Sciences, Physical Chemistry, 1.1 Normal biological development and functioning, Binding Sites, Crystallization, Electrochemistry, Freezing, Hydroxides, Magnesium, Models, Molecular, Molecular Structure, Nucleic Acid Conformation, RNA, Catalytic, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Developmental Biology, Biological sciences, Chemical sciences, Environmental sciences
Abstract

In the presence of magnesium ions, cleavage by the hammerhead ribozyme RNA at a specific residue leads to 2'3'-cyclic phosphate and 5'-OH extremities. In the cleavage reaction an activated ribose 2'-hydroxyl group attacks its attached 3'-phosphate. Molecular dynamics simulations of the crystal structure of the hammerhead ribozyme, obtained after flash-freezing of crystals under conditions where the ribozyme is active, provide evidence that a mu-bridging OH-ion is located between two Mg2+ions close to the cleavable phosphate. Constrained simulations show further that a flip from the C3'- endo to the C2'- endo conformation of the ribose at the cleavable phosphate brings the 2'-hydroxyl in proximity to both the attacked phosphorous atom and the mu-bridging OH-ion. Thus, the simulations lead to a detailed new insight into the mechanism of hammerhead ribozyme cleavage where a mu-hydroxo bridged magnesium cluster, located on the deep groove side, provides an OH-ion that is able to activate the 2'-hydroxyl nucleophile after a minor and localized conformational change in the RNA.

Published
1997

21. Dinucleotide TpT and its 2'-O-Me analogue possess different backbone conformations and flexibilities but similar stacked geometries

Author

Santini, Guillaume P.H., Pakleza, Christophe, Auffinger, Pascal, Moriou, Celine, Favre, Alain, Clivio, Pascale, and Cognet, Jean A.H.

Subjects
Nucleotides -- Research, Quantum chemistry -- Research, Photochemical research, Chemicals, plastics and rubber industries
Abstract

The computed average stacked conformations of 2'-O,5-dimethyluridylyl(3'-5')-2'-O,5-dimethyluridine and of natural thymidylyl(3'-5')thymidine which could serve as starting models to investigate photochemical reactions with quantum dynamics simulations are presented.

Published
2007

30. Molecular dynamics simulations of the anticodon hairpin of tRNA(superAsp): structuring effects of C-H...O hydrogen bonds and of long-range hydration forces

Author

Auffinger, Pascal, Louise-May, Shirley, and Westhof, Eric

Subjects
Amino acids -- Research, Molecular dynamics -- Models, Transfer RNA -- Research, Chemistry
Abstract

The effects of long-range hydration forces on system, structural stabilization and solute dynamics of the anticodon hairpin of tRNA(superAsp) were investigated by calculating all the solute-solute interactions based on MD trajectories. The effect of carbon-hydrogen bonds on the tertiary native conformation of the molecule was verified and characterized. The results showed that long-ranged solvation forces influence the stabilization of highly charged nucleic acid systems.

Published
1996

33. Multiple molecular dynamics simulations of the anticodon loop of tRNA(super Asp) in aqueous solution with counterions

Author

Auffinger, Pascal, Lousie-May, Shirley, and Westhof, Eric

Subjects
Transfer RNA -- Analysis, Simulation methods -- Usage, Molecular dynamics -- Methods, Chemistry
Abstract

A nanosecond of molecular dynamics (MD) simulation on the solvated anticodon loop of tRNA(super Asp) is analyzed, directing to address the ramifications of the detected differences in ten 100 ps molecular dynamics trajectories produced by modifying initial protocol of the systems. The resulting divergent trajectories differ in structural and dynamical characteristics. No relation exists between the modifications made in the system and the properties of the trajectories. The multiple MD recognized the protocol stability.

Published
1995

38. A comprehensive classification and nomenclature of carboxyl–carboxyl(ate) supramolecular motifs and related catemers: implications for biomolecular systems

Author

D’Ascenzo, Luigi and Auffinger, Pascal

Subjects
Pharmaceutical Preparations, crystal engineering, biomolecular systems, Carboxylic Acids, Molecular Conformation, Hydrogen Bonding, pharmaceuticals, Research Papers, supramolecular motifs, Dimerization
Abstract

The vast diversity of carboxyl–carboxyl(ate) arrangements is reduced to 17 supramolecular motifs and eight catemers. Examples of each, extracted from the CSD, are presented., Carboxyl and carboxylate groups form important supramolecular motifs (synthons). Besides carboxyl cyclic dimers, carboxyl and carboxylate groups can associate through a single hydrogen bond. Carboxylic groups can further form polymeric-like catemer chains within crystals. To date, no exhaustive classification of these motifs has been established. In this work, 17 association types were identified (13 carboxyl–carboxyl and 4 carboxyl–carboxylate motifs) by taking into account the syn and anti carboxyl conformers, as well as the syn and anti lone pairs of the O atoms. From these data, a simple rule was derived stating that only eight distinct catemer motifs involving repetitive combinations of syn and anti carboxyl groups can be formed. Examples extracted from the Cambridge Structural Database (CSD) for all identified dimers and catemers are presented, as well as statistical data related to their occurrence and conformational preferences. The inter-carboxyl(ate) and carboxyl(ate)–water hydrogen-bond properties are described, stressing the occurrence of very short (strong) hydrogen bonds. The precise characterization and classification of these supramolecular motifs should be of interest in crystal engineering, pharmaceutical and also biomolecular sciences, where similar motifs occur in the form of pairs of Asp/Glu amino acids or motifs involving ligands bearing carboxyl(ate) groups. Hence, we present data emphasizing how the analysis of hydrogen-containing small molecules of high resolution can help understand structural aspects of larger and more complex biomolecular systems of lower resolution.

Published
2015

44. Deflating the RNA Mg2+bubble: stereochemistry to the rescue!

Author

Auffinger, Pascal, Ennifar, Eric, and D'Ascenzo, Luigi

Abstract

Proper evaluation of the ionic structure of biomolecular systems through X-ray and cryo-EM techniques remains challenging but is essential for advancing our understanding of the underlying structure/activity/solvent relationships. However, numerous studies overestimate the number of Mg2+in deposited structures due to assignment errors finding their origin in improper consideration of stereochemical rules. Herein, to tackle such issues, we reevaluate the PDBid 6QNR and 6SJ6 models of the ribosome ionic structure. We establish that stereochemical principles need to be carefully pondered when examining ion binding features, even when K+anomalous signals are available as is the case for the 6QNR PDB entry. For ribosomes, assignment errors can result in misleading conceptions of their solvent structure. For instance, present stereochemical analysis results in a significant decrease of the number of assigned Mg2+in 6QNR, suggesting that K+and not Mg2+is the prevalent ion in the ribosome first solvation shell. We stress that the use of proper stereochemical guidelines in combination or not with other identification techniques, such as those pertaining to the detection of transition metals, of some anions and of K+anomalous signals, is critical for deflating the current Mg2+bubble witnessed in many ribosome and other RNA structures. We also stress that for the identification of lighter ions such as Mg2+, Na+, …, for which no anomalous signals can be detected, stereochemistry coupled with high resolution structures (<2.4 Å) remains the best currently available option.

Published
2021
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