title: Structure- and ligand-based virtual screening identifies new scaffolds for inhibitors of the oncoprotein MDM2.
abstract: A major challenge in the field of ligand discovery is to identify chemically useful fragments that can be developed into inhibitors of specific protein-protein interactions. Low molecular weight fragments (with molecular weight less than 250 Da) are likely to bind weakly to a protein's surface. Here we use a new virtual screening procedure which uses a combination of similarity searching and docking to identify chemically tractable scaffolds that bind to the p53-interaction site of MDM2. The binding has been verified using capillary electrophoresis which has proven to be an excellent screening method for such small, weakly binding ligands.
authors.affiliation: Institute of Structural and Molecular Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Houston
authors.affiliation: Institute of Structural and Molecular Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Li-Hsuan
authors.initials: LH
authors.lastname: Yen
authors.affiliation: Selcia Limited, Fyfield Business & Research Park, Ongar, Essex, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Pettit
authors.affiliation: Institute of Structural and Molecular Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Walkinshaw
mesh_terms: D001665:Binding Sites; D019075:Electrophoresis, Capillary; D005454:Fluorescence Polarization; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism
chemical_list: D007093:Imidazoles; D008024:Ligands; D010879:Piperazines; D054852:Small Molecule Libraries; C482205:nutlin 3; D051736:Proto-Oncogene Proteins c-mdm2