title: Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41.
abstract: Recent experimental study found that OLE (olive leaf extract) has anti-HIV activity by blocking the HIV virus entry to host cells [Lee-Huang, S., Zhang, L., Huang, P.L., Chang, Y. and Huang, P.L. (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem. Biophys. Res. Commun. 307, 1029; Lee-Huang, S., Huang, P.L., Zhang, D., Lee, J.W., Bao, J., Sun, Y., Chang, Y.-Tae, Zhang, J.Z.H. and Huang, P.L. (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol. Biochem. Biophys. Res. Commun. 354, 872-878, 879-884]. As part of a joint experimental and theoretical effort, we report here computational study to help identify and characterize the binding complexes of several main compounds of OLE (olive leaf extract) to HIV-1 envelop protein gp41. A number of possible binding modes are found by docking oleuropein and its metabolites, aglycone, elenolic acid and hydroxytyrosol, onto the hydrophobic pocket on gp41. Detailed OLE-gp41 binding interactions and free energies of binding are obtained through molecular dynamics simulation and MM-PBSA calculation. Specific molecular interactions in our predicted OLE/gp41 complexes are identified and hydroxytyrosol is identified to be the main moiety for binding to gp41. This computational study complements the corresponding experimental investigation and helps establish a good starting point for further refinement of OLE-based gp41 inhibitors.
authors.affiliation: Department of Chemistry, New York University, New York, NY 10003, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bao
authors.forename: D W
authors.initials: DW
authors.lastname: Zhang
authors.forename: J Z H
authors.initials: JZ
authors.lastname: Zhang
authors.forename: P Lee
authors.initials: PL
authors.lastname: Huang
authors.forename: P Lin
authors.initials: PL
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Lee-Huang
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003198:Computer Simulation; D015700:HIV Envelope Protein gp41 / Q000737:chemistry* / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D057888:Iridoid Glucosides; D039823:Iridoids; D008958:Models, Molecular; D015394:Molecular Structure; D031658:Olea / Q000737:chemistry*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D011485:Protein Binding; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D057888:Iridoid Glucosides; D039823:Iridoids; D010936:Plant Extracts; D011714:Pyrans; C005975:3,4-dihydroxyphenylethanol; C002769:oleuropein; C000352:elenolic acid; D010626:Phenylethyl Alcohol