Ribosomal RNA-Aminoglycoside Hygromycin B Interaction Energy Calculation within a DFT Framework.

Abstract

We intend to investigate the drug-binding energy of each nucleotide inside the aminoglycoside hygromycin B (hygB) binding site of 30S ribosomal RNA (rRNA) subunit by using the Molecular Fractionation with Conjugate Caps (MFCC) strategy based on the Density Functional Theory (DFT), considering the functional LDA/PWC, OBS and the dielectric constant parametrization. Aminoglycosides are bactericidal antibiotics that have high affinity to the prokaryotic ribosomal RNA, inhibiting the synthesis of proteins by acting on the main stages of the translation mechanism, whereas binding to rRNA 16S, a component of the 30S ribosomal subunit in prokaryotes. The identification of the nucleotides presenting the most negative binding energies allows us to stabilize hygB in a suitable binding pocket of 30S ribosomal subunit. In addition, it should highlighted that mutations in these residues may probably lead to resistance to ribosome-targeting antibiotics. Quantum calculations of aminoglycoside hygromycin B-ribosome complex might contribute to further quantum studies with antibiotics like macrolides and other aminoglycosides.