Evaluation of a Semi-Automated Workflow for Fragment Growing

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.