Templates for design of inhibitors for serine proteases: application of the program DOCK to the discovery of novel inhibitors for thrombin.
The program DOCK was used to search for novel inhibitors for alpha-thrombin. Four among the top twelve best scoring compounds from the Cambridge Structural Data Base inhibited this enzyme, and three of them inhibited alpha-thrombin in a competitive mode. These molecules are expected to serve as general templates for structural elaboration in targeting diverse serine proteases for selective inhibition.
Massova
I
I
Department of Chemistry, Wayne State University, Detroit, MI 48202-3489, USA.
Martin
P
P
Bulychev
A
A
Kocz
R
R
Doyle
M
M
Edwards
B F
BF
Mobashery
S
S
D001665:Binding Sites; D016208:Databases, Factual; D015195:Drug Design; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis*; D012984:Software; D013698:Templates, Genetic; D013917:Thrombin / Q000037:antagonists & inhibitors*
D015842:Serine Proteinase Inhibitors; D013917:Thrombin