The effect of tightly-bound water molecules on scaffold diversity in computer-aided de novo ligand design of CDK2 inhibitors
MetadataShow full item record
We have determined the effects that tightly bound water molecules have on the de novo design of cyclin-dependent kinase-2 (CDK2) ligands. In particular, we have analyzed the impact of a specific structural water molecule on the chemical diversity and binding mode of ligands generated through a de novo structure-based ligand generation method in the binding site of CDK2. The tightly bound water molecule modifies the size and shape of the binding site and we have found that it also imposed constraints on the observed binding modes of the generated ligands. This in turn had the indirect effect of reducing the chemical diversity of the underlying molecular scaffolds that were able to bind to the enzyme satisfactorily.
Showing items related by title, author, creator and subject.
Including Tightly-Bound Water Molecules in de Novo Drug Design. Exemplification through the in Silico Generation of Poly(ADP-ribose)polymerase LigandsMancera, Ricardo; Garcia-Sosa, A.; Firth-Clark, S. (2005)Different strategies for the in silico generation of ligand molecules in the binding site of poly(ADP-ribose)-polymerase (PARP) were studied in order to observe the effect of the targeting and displacement of tightly bound ...
Urolithiasis: occurrence and function of intracrystalline proteins in calcium oxalate monohydrate crystalsFleming, David Elliot (2004)The broad aim of the work presented in this thesis was to examine the relationship between the mineral and organic phases of calcium oxalate monohydrate (COM) crystals, which are the principal components of human kidney ...
Yuriev, E.; Agostino, Mark; Ramsland, P. (2011)Docking is a computational technique that places a small molecule (ligand) in the binding site of its macromolecular target (receptor) and estimates its binding affinity. This review addresses methodological developments ...