Volume 50, Number 2, April-June 2016
Special issue: Recent Advances in Operations Research in Computational Biology, Bioinformatics and Medicine
|Page(s)||375 - 386|
|Published online||28 March 2016|
Structural and energetic comparison of the complexes of aminoglycosides with the model of the ribosomal A-site∗,∗∗
1 Centre of New Technologies,
University of Warsaw, Banacha 2c, 02-097
2 Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Accepted: 21 September 2015
Understanding the interactions which govern aminoglycoside antibiotic binding to ribosomal RNA is essential to propose modifications of these antibiotics. We have investigated the hydrogen bond patterns, solvent accessibility, and stacking energies of the nucleobases in twelve different aminoglycoside-RNA crystal complexes. These analyses pointed to some antibiotic-induced RNA structural differences that depend on the type of bound aminoglycoside. The largest differences were in the hydrogen bonding pattern in the vicinity of the U1406 and U1495 base pairs, especially in the complexes with geneticin and modified paromomycin. The complexes that stand out were the ones with neamine and kanamycin. We found that the solvent-accessible surface area buried upon aminoglycoside binding to RNA increases with the number of aminoglycoside rings but its correlation with the net charge of the antibiotic or experimental binding free energies was weak. We also investigated the dependence of other aminoglycoside characterizing descriptors, such as the number of rings and total charge, on the experimentally determined Gibbs energies. The correlation of ΔG with the total charge had the coefficient of determination R2 over 0.8–0.9, depending on experimental data set, and was the highest of all descriptors.
Mathematics Subject Classification: 92C05 / 92C40
Key words: Aminoglycosides / ribosomal RNA / A-site / solvent accessible surface area / hydrogen bonds / nucleobase stacking
© EDP Sciences, ROADEF, SMAI 2016
Current usage metrics show cumulative count of Article Views (full-text article views including HTML views, PDF and ePub downloads, according to the available data) and Abstracts Views on Vision4Press platform.
Data correspond to usage on the plateform after 2015. The current usage metrics is available 48-96 hours after online publication and is updated daily on week days.
Initial download of the metrics may take a while.