abstract
Ribonucleic acids (RNAs) have only recently been viewed as a target for small-molecules drug discovery. Aminoglycoside compounds are antibiotics which bind the ribosomal A site (16S fragment) and cause misreading of the bacterial genetic code and inhibit translocation. In this work, a complete molecular modeling study is done for 16 newly derived anninoglycoside compounds where diverse nucleoside fragments are linked. Docking calculations are applied to 16S RNA target and a weak linear correlation, between experimental and calculated data, is obtained. However, one particularity of RNA is its high flexibility. To mimic this behavior, all docking calculations are followed by small molecular dynamic simulations. This last computational step improves significantly the correlation with experimental data and allowed us to establish structure-activity relationships. The overall results showed that the consideration of the RNA dynamic behavior is of great interest. (c) 2007 Elsevier Masson SAS. All rights reserved.
keywords
AMBER FORCE-FIELD; MOLECULAR-DYNAMICS; DRUG TARGET; MECHANICAL CALCULATIONS; CATIONIC ANTIBIOTICS; A-SITE; BINDING; PROTEINS; MODEL; SIMULATIONS
subject category
Pharmacology & Pharmacy
authors
Barbault, F; Ren, B; Rebehmed, J; Teixeira, C; Luo, Y; Smila-Castro, O; Maurel, F; Fan, BT; Zhang, LR; Zhang, LH
our authors
Cátia Teixeira
Post-doc FellowshipGroups
acknowledgements
The works of the Ph.D. students are supported by various fellowships: Joseph Rebehmed from the French Ministry of Research and Technology, Catia Teixeira from the