title: Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.
abstract: The history of fragment-based drug discovery, with an emphasis on crystallographic methods, is sketched, illuminating various contributions, including our own, which preceded the industrial development of the method. Subsequently, the creation of the BMSC fragment cocktails library is described. The BMSC collection currently comprises 68 cocktails of 10 compounds that are shape-wise diverse. The utility of these cocktails for initiating lead discovery in structure-based drug design has been explored by soaking numerous protein crystals obtained by our MSGPP (Medical Structural Genomics of Pathogenic Protozoa) consortium. Details of the fragment selection and cocktail design procedures, as well as examples of the successes obtained are given. The BMSC Fragment Cocktail recipes are available free of charge and are in use in over 20 academic labs.
authors.affiliation: Medical Structural Genomics of Pathogenic Protozoa, University of Washington, Seattle, WA 98195, USA. verlinde@u.washington.edu
authors.forename: Christophe L M J
authors.initials: CL
authors.lastname: Verlinde
authors.forename: Erkang
authors.initials: E
authors.lastname: Fan
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shibata
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ross
authors.forename: Jessica
authors.initials: J
authors.lastname: Kim
authors.forename: Liren
authors.initials: L
authors.lastname: Xiao
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Arakaki
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bosch
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Caruthers
authors.forename: Eric T
authors.initials: ET
authors.lastname: Larson
authors.forename: Isolde
authors.initials: I
authors.lastname: Letrong
authors.forename: Alberto
authors.initials: A
authors.lastname: Napuli
authors.forename: Angela
authors.initials: A
authors.lastname: Kelly
authors.forename: Natasha
authors.initials: N
authors.lastname: Mueller
authors.forename: Frank
authors.initials: F
authors.lastname: Zucker
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Van Voorhis
authors.forename: Frederick S
authors.initials: FS
authors.lastname: Buckner
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Merritt
authors.forename: Wim G J
authors.initials: WG
authors.lastname: Hol
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D018503:Genome, Protozoan; D006801:Humans; D011528:Protozoan Infections / Q000188:drug therapy*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D054852:Small Molecule Libraries