Exhaustive de novo design of low-molecular-weight fragments against the ATP-binding site of DNA-gyrase.
We present a de novo design approach to generating small fragments in the DNA-gyrase ATP-binding site using the computational drug design platform SkelGen. We have generated an exhaustive number of structural possibilities, which were subsequently filtered for site complementarity and synthetic tractability. A number of known active fragments are found, but most of the species created are potentially novel and could be valuable for further elaboration and development into lead-like structures.
Firth-Clark
Stuart
S
De Novo Pharmaceuticals Ltd., Compass House, Vision Park, Histon, Cambridge CB4 9ZR, U.K. stuart.firth-clark@denovopharma.com
Todorov
Nikolay P
NP
Alberts
Ian L
IL
Williams
Anthony
A
James
Timothy
T
Dean
Philip M
PM
D000255:Adenosine Triphosphate / Q000378:metabolism*; D001665:Binding Sites; D027081:DNA Gyrase / Q000378:metabolism*; D015195:Drug Design; D008970:Molecular Weight
D000255:Adenosine Triphosphate; D027081:DNA Gyrase