Dr Giovanna Tedesco presented presented A picture tells a thousand words: Using activity cliffs maps to understand SAR. She focused on the combined use of activity cliffs analysis, as implemented in Activity Atlas and Activity Miner, as a useful method to analyze the Structure-Activity Relationships (SAR) of data sets of different size and complexity.
Summarizing SAR into simple, interpretable maps
Activity Atlas is a novel, qualitative method available in Forge, Cresset’s powerful workbench for ligand design and SAR analysis. It uses a probabilistic approach to take a global view of the data in a qualitative manner, analyzing the SAR of a set of aligned compounds as a function of their 3D electrostatic, hydrophobic and shape properties. Results are displayed as highly visual 3D activity cliffs summary maps that give an overview of the SAR landscape, focusing on the prevalent SAR signals.
Rapid navigation of complex SAR, highlighting key activity changes
Activity Miner, a module of Forge (and optional module in Torch), enables rapid navigation of activity cliffs. It can be used to drill down into the Activity Atlas maps and understand subtle molecule-to-molecule structure-activity changes, identifying potential outliers and giving concrete examples of changes that generate the summary.
The information derived from these analyses is an invaluable aid for drug discovery projects that help to inform design decisions and prioritize new molecules for synthesis.
The application of the methods presented was illustrated on example data sets of different size and complexity taken from the literature. The case studies shown include:
- SAR analysis of a small set of 7 sodium channel antagonists
- SAR analysis of Orexin 2 receptor ligands US patent data
- Selectivity analysis of adenosine A1, A2a and A3 antagonists through multiple activities.
Cresset seminar at Chem-Bio Informatics Society Annual Meeting 2016, Japan
Cresset stand at Chem-Bio Informatics Society Annual Meeting 2016, Japan