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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

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

Revista

Título: European Journal of Medicinal Chemistry

Vol. 43 Nº 4

Páginas: 1648-1656

ISSN: 0223-5234

Editora: Elsevier

Indexação

ISI Web of Knowledge - 16 Citações

Scopus - 13 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9