Flexible computational docking studies of new aminoglycosides targeting RNA 16S bacterial ribosome site

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Barbault, F (Author) Other; Ren, B (Author) Other; Rebehmed, J (Author) Other; Catia Teixeira (Author) Other; Luo, Y (Author) Other; Smila Castro, O (Author) Other; Maurel, F (Author) Other; Fan, BT (Author) Other; Zhang, LR (Author) Other; Zhang, LH (Author) Other

Journal

Title: European Journal of Medicinal Chemistry

Vol. 43 No. 4

Pages: 1648-1656

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 16 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-008-TC3

DOI: 10.1016/j.ejmech.2007.10.022

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9