title: Molecular docking programs successfully predict the binding of a beta-lactamase inhibitory protein to TEM-1 beta-lactamase.
abstract: Crystallization of the 1:1 molecular complex between the beta-lactamase TEM-1 and the beta-lactamase inhibitory protein BLIP has provided an opportunity to put a stringent test on current protein-docking algorithms. Prior to the successful determination of the structure of the complex, nine laboratory groups were given the refined atomic coordinates of each of the native molecules. Other than the fact that BLIP is an effective inhibitor of a number of beta-lactamase enzymes (KI for TEM-1 approximately 100 pM) no other biochemical or structural data were available to assist the practitioners in their molecular docking. In addition, it was not known whether the molecules underwent conformational changes upon association or whether the inhibition was competitive or non-competitive. All six of the groups that accepted the challenge correctly predicted the general mode of association of BLIP and TEM-1.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: N C
authors.initials: NC
authors.lastname: Strynadka
authors.forename: M
authors.initials: M
authors.lastname: Eisenstein
authors.forename: E
authors.initials: E
authors.lastname: Katchalski-Katzir
authors.forename: B K
authors.initials: BK
authors.lastname: Shoichet
authors.forename: I D
authors.initials: ID
authors.lastname: Kuntz
authors.forename: R
authors.initials: R
authors.lastname: Abagyan
authors.forename: M
authors.initials: M
authors.lastname: Totrov
authors.forename: J
authors.initials: J
authors.lastname: Janin
authors.forename: J
authors.initials: J
authors.lastname: Cherfils
authors.forename: F
authors.initials: F
authors.lastname: Zimmerman
authors.forename: A
authors.initials: A
authors.lastname: Olson
authors.forename: B
authors.initials: B
authors.lastname: Duncan
authors.forename: M
authors.initials: M
authors.lastname: Rao
authors.forename: R
authors.initials: R
authors.lastname: Jackson
authors.forename: M
authors.initials: M
authors.lastname: Sternberg
authors.forename: M N
authors.initials: MN
authors.lastname: James
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D005973:Glutamine; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D015203:Reproducibility of Results; D001618:beta-Lactamases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C065596:beta-lactamase-inhibitor protein, Streptomyces; D005973:Glutamine; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1