title: CONFIRM: connecting fragments found in receptor molecules.
abstract: A novel algorithm for the connecting of fragment molecules is presented and validated for a number of test systems. Within the CONFIRM (Connecting Fragments Found in Receptor Molecules) approach a pre-prepared library of bridges is searched to extract those which match a search criterion derived from known experimental or computational binding information about fragment molecules within a target binding site. The resulting bridge 'hits' are then connected, in an automated fashion, to the fragments and docked into the target receptor. Docking poses are assessed in terms of root-mean-squared deviation from the known positions of the fragment molecules, as well as docking score should known inhibitors be available. The creation of the bridge library, the full details and novelty of the CONFIRM algorithm, and the general applicability of this approach within the field of fragment-based de novo drug design are discussed.
authors.affiliation: Wyeth Research, Chemical and Screening Sciences, 200 CambridgePark Drive, Cambridge, MA, 02140, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Thompson
authors.forename: R Aldrin
authors.initials: RA
authors.lastname: Denny
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Nilakantan
authors.forename: Christine
authors.initials: C
authors.lastname: Humblet
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
authors.forename: Eric
authors.initials: E
authors.lastname: Feyfant
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000737:chemistry / Q000378:metabolism; D019809:Streptavidin / Q000737:chemistry
chemical_list: D008024:Ligands; D020033:Protein Isoforms; D011506:Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D019809:Streptavidin