title: Exhaustive de novo design of low-molecular-weight fragments against the ATP-binding site of DNA-gyrase.
abstract: 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.
authors.affiliation: De Novo Pharmaceuticals Ltd., Compass House, Vision Park, Histon, Cambridge CB4 9ZR, U.K. stuart.firth-clark@denovopharma.com
authors.forename: Stuart
authors.initials: S
authors.lastname: Firth-Clark
authors.forename: Nikolay P
authors.initials: NP
authors.lastname: Todorov
authors.forename: Ian L
authors.initials: IL
authors.lastname: Alberts
authors.forename: Anthony
authors.initials: A
authors.lastname: Williams
authors.forename: Timothy
authors.initials: T
authors.lastname: James
authors.forename: Philip M
authors.initials: PM
authors.lastname: Dean
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001665:Binding Sites; D027081:DNA Gyrase / Q000378:metabolism*; D015195:Drug Design; D008970:Molecular Weight
chemical_list: D000255:Adenosine Triphosphate; D027081:DNA Gyrase