title: Evaluation of a semi-automated workflow for fragment growing.
abstract: Intelligent Automatic Design (IADE) is an expert system developed at Novartis to identify nonclassical bioisosteres. In addition to bioisostere searching, one could also use IADE to grow a fragment bound to a protein. Here we report an evaluation of IADE as a tool for fragment growing. Three examples from the literature served as test cases. In all three cases, IADE generated close analogues of the published compounds and reproduced their crystallographic binding modes. This exercise validated the use of the IADE system for fragment growing. We have also gained experience in optimizing the performance of IADE for this type of application.
authors.affiliation: Novartis Institutes for BioMedical Research , Novartis Campus, CH-4056 Basel, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirard
authors.forename: Peter
authors.initials: P
authors.lastname: Ertl
mesh_terms: D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D017076:Computer-Aided Design; D003461:Crystallography; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D047495:PPAR gamma / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D057188:Workflow; D048051:p38 Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D008024:Ligands; D047495:PPAR gamma; D011506:Proteins; D048051:p38 Mitogen-Activated Protein Kinases