In drug discovery programs, summarizing and understanding the SAR for large data sets of compounds can be a difficult and time-consuming exercise. It is often the responsibility of the computational chemist supporting the project team to carry out this analysis, sharing the results with medicinal chemists in a clear and concise manner, to inform new molecule design and help them define the future directions of the project. With Activity Atlas you can easily summarize complex SAR into a visual 3D map, condensing a large table of data into a single picture. It is a probabilistic method of analyzing the Structure-activity relationships of a set of aligned compounds as a function of their electrostatic and shape properties. The method uses a Bayesian approach to take a global view of the data in a qualitative manner, taking into account the probability that a molecule is correctly aligned. Activity Atlas generates three distinct maps of the electrostatic, shape and hydrophobic properties around molecules. The activity cliffs summary looks at all the molecules in the data set, maps their field differences, and creates a single picture of how changes in the shape and electrostatic properties of the molecules affect their activity. The average of actives model looks at all active molecules, maps their fields and helps you determine which electrostatic, shape and hydrophobic features are most important for activity. Finally, the regions explored analysis provides a view of which parts of the property space around a molecule have been adequately explored. Additionally, when considering a new molecule for synthesis, it computes an ‘information content’ score for the new molecule, answering the following question: if we made and tested this new molecule, how much would it actually increase the SAR information content of the data set? Activity Atlas visual 3D maps provide an invaluable tool for computational chemists to help medicinal chemists improve the physico-chemical profile of the newly designed compounds, while maintaining the biological activity of interest

Picture tells a thousand words: Summarizing SAR for medicinal chemists

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.