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Article Dans Une Revue Theoretical Chemistry Accounts: Theory, Computation, and Modeling Année : 1998

MCSS-based predictions of RNA binding sites

Fabrice Leclerc

Résumé

The diversity of RNA tertiary structures provides the basis for speci®c recognition by proteins or small molecules. To investigate the structural basis and the energetics which control RNA-ligand interactions, favorable RNA binding sites are identi®ed using the MCSS method, which has been employed previously only for protein receptors. Two dierent RNAs for which the structures have been determined by NMR spectroscopy were examined: two structures of the TAR RNA which contains an arginine binding site, and the structure of the 16S rRNA which contains an aminoglycoside binding site (paromomycin). In accord with the MCSS methodology, the functional groups representing the entire ligand or only part of it (one residue in the case of the aminoglycosides) are ®rst replicated and distributed with random positions and orientations around the target and then energy minimized in the force ®eld of the target RNA. The Coulombic term and the dielectric constant of the force ®eld are adjusted to approximate the eects of solvent-screening and counterions. Optimal force ®eld parameters are determined to reproduce the binding mode of arginine to the TAR RNA. The more favorable binding sites for each residue of the aminoglycoside ligands are then calculated and compared with the binding sites observed experimentally. The predictability of the method is evaluated and re®nements are proposed to improve its accuracy.

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hal-03992529 , version 1 (16-02-2023)

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Fabrice Leclerc, Martin Karplus. MCSS-based predictions of RNA binding sites. Theoretical Chemistry Accounts: Theory, Computation, and Modeling, 1998, 101, pp.131-137. ⟨10.1007/s002140050419⟩. ⟨hal-03992529⟩
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