title: A molecular dynamics simulation study of an aminoglycoside/A-site RNA complex: conformational and hydration patterns.
abstract: Aminoglycoside antibiotics interfere with the translation mechanism by binding to the tRNA decoding site of the 16S ribosomal RNA. Crystallographic structures of aminoglycosides bound to A-site systems clarified many static aspects of RNA-ligand interactions. To gain some insight on the dynamic aspects of recognition phenomena, we conducted molecular dynamics simulations of the aminoglycoside paromomycin bound to a eubacterial ribosomal decoding A-site oligonucleotide. Results from 25 ns of simulation time revealed that: (i) the neamine part of the antibiotic represents the main anchor for binding, (ii) additional sugar rings provide limited and fragile contacts, (iii) long-resident water molecules present at the drug/RNA interface are involved in the recognition phenomena. The combination of MD simulations together with systematic structural information offers striking insights into the molecular recognition processes underlying RNA/aminoglycoside binding. Important methodological considerations related to the use of medium resolution starting structures and associated sampling problems are thoroughly discussed.
authors.affiliation: Institut de biologie moléculaire et cellulaire du CNRS, modélisation et simulations des acides nucléiques, UPR 9002, 15, rue René-Descartes, 67084 Strasbourg cedex, France.
authors.forename: A C
authors.initials: AC
authors.lastname: Vaiana
authors.forename: E
authors.initials: E
authors.lastname: Westhof
authors.forename: P
authors.initials: P
authors.lastname: Auffinger
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray / Q000379:methods; D008958:Models, Molecular; D009690:Nucleic Acid Conformation / Q000187:drug effects; D010303:Paromomycin / Q000737:chemistry / Q000494:pharmacology; D012336:RNA, Ribosomal, 16S / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D010303:Paromomycin