title: Molecular modeling study on the enantioselective binding of S- and R-ofloxacin to various DNA sequences.
abstract: The complex formation of S- and R-ofloxacin with the self-complementary oligonucleotides, namely d[ATAGCGCTAT](2), d[GCGATATCGC](2) and d[ATAICICTAT](2), were investigated by the molecular dynamics (MD) simulation. Four starting positions, including two intercalation positions with different insertion directions and two minor groove binding positions, were considered. The total energy of both S- and R-ofloxacin-d[ATAGCGCTAT](2) complex, in which ofloxacin binds in the minor groove of the oligonucleotide, were lower than any intercalation binding mode. For both enantiomers, formation of the complex with GC oligonucleotide is more favorable than AT and IC oligonucleotides. When S- and R-ofloxacin are compared, the S-enantiomer exhibits more favorable total energy and torsion angles in the complex formation. This result is in agreement with the experimental observation [Hwangbo et al., Eur J Pharm Sci 18, 197 (2003)]. In the complex, both enantiomers form two hydrogen bonds: one between the carbonyl group of ofloxacin and the amine group of G16 and the other between the fluorine group and the G6 amine for S-ofloxacin. However, only one hydrogen bond is formed between endocyclic hydrogen atom at the C2 position of adenine and inosine base and carbonyl group of ofloxacin, which may be the reason for the GC preferentiality of ofloxacin.
authors.affiliation: Department of Chemistry, Yeungnam University, Daedong, Gyeongsan City, Gyeong-buk 712-749, Republic of Korea.
authors.forename: Hyun Mee
authors.initials: HM
authors.lastname: Lee
authors.forename: Hye Dong
authors.initials: HD
authors.lastname: Kim
authors.forename: Jong Moon
authors.initials: JM
authors.lastname: Kim
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Seog K
authors.initials: SK
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D001667:Binding, Competitive; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism; D015242:Ofloxacin / Q000737:chemistry* / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D004247:DNA; D015242:Ofloxacin