Intelligent Automatic Design of Bioisosteric Analogs

A program for automatic identification of bioisosteric analogs, scaffold hopping and fragment growing called IADE has been developed at Novartis Institutes for BioMedical Research. The system frees modelers from repetitive and time consuming tasks and allows them spend more time on creative work: evaluating and selecting the best ideas from automatically designed structures.

Cresset’s command line FieldAlign (now part of Forge) software was used by Novartis as follows:

• To generate a set of representative conformations using standard methods from which the conformation most similar to the template ligand is identified.
• To find the best alignment based on superposition of positive, negative, hydrophobic and steric fields around the molecules.
• For similarity scoring (employing an equal weighting of field and shape similarities).
• For conformation search and subsequent identification of the most similar conformer.

Novartis’ work has been published in J. Comput. Aided Mol. Des, 26, 1207-1215 (2012) and can be read here.

Peter Ertl, Novartis and co-author of the above article, was the winner of Cresset’s Design a Molecule Competition in Fall 2011 and presented the work at Cresset’s 2012 European User Meeting.

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