Fragment-based cocktail crystallography by the medical structural genomics of pathogenic protozoa consortium.
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.
Verlinde
Christophe L M J
CL
Medical Structural Genomics of Pathogenic Protozoa, University of Washington, Seattle, WA 98195, USA. verlinde@u.washington.edu
Fan
Erkang
E
Shibata
Sayaka
S
Zhang
Zongsheng
Z
Sun
Zhihua
Z
Deng
Wei
W
Ross
Jennifer
J
Kim
Jessica
J
Xiao
Liren
L
Arakaki
Tracy L
TL
Bosch
Jürgen
J
Caruthers
Jonathan M
JM
Larson
Eric T
ET
Letrong
Isolde
I
Napuli
Alberto
A
Kelly
Angela
A
Mueller
Natasha
N
Zucker
Frank
F
Van Voorhis
Wesley C
WC
Buckner
Frederick S
FS
Merritt
Ethan A
EA
Hol
Wim G J
WG
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
D054852:Small Molecule Libraries