title: Binding of aminoglycoside antibiotics to the small ribosomal subunit: a continuum electrostatics investigation.
abstract: The binding of paromomycin and similar antibiotics to the small (30S) ribosomal subunit has been studied using continuum electrostatics methods. Crystallographic information from a complex of paromomycin with the 30S subunit was used as a framework to develop structures of similar antibiotics in the same ribosomal binding site. Total binding energies were calculated from electrostatic properties obtained by solution of the Poisson-Boltzmann equation combined with a surface area-dependent apolar term. These computed results showed good correlation with experimental data. Additionally, calculation of the ribosomal electrostatic potential in the paromomycin binding site provided insight into the electrostatic mechanisms for aminoglycoside binding and clues for the rational design of more effective antibiotics.
authors.affiliation: Department of Chemistry, Yale University, New Haven, Connecticut 06520, USA. chiansan@yale.edu
authors.forename: Chiansan
authors.initials: C
authors.lastname: Ma
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Baker
authors.forename: Simpson
authors.initials: S
authors.lastname: Joseph
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D007700:Kinetics; D008958:Models, Molecular; D009355:Neomycin / Q000737:chemistry / Q000378:metabolism; D010303:Paromomycin / Q000737:chemistry / Q000378:metabolism; D012336:RNA, Ribosomal, 16S / Q000737:chemistry* / Q000378:metabolism*; D012271:Ribostamycin / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D012271:Ribostamycin; D010303:Paromomycin; D009355:Neomycin