Visualising lead optimisation series using reduced graphs
This month’s paper of the month has been recently published by our Senior Computational Chemist, Jess Stacey, for her PhD work that she undertook at the University of Sheffield. They were using Reduced Graphs (RG) to visualise lead optimisation series, indicating areas that have been over- or underexplored, whilst focusing on key interactions too.
In the paper, they outline how they calculate the RGs themselves, how they extract the RG cores, how they map the RG cores back onto the original RGs and then how they use pie charts for each RG node to represent the level of exploration at each node. The method is then used on a ChEMBL P2X7 receptor GSK subset to demonstrate how this method can be used on real-life examples. Thirteen RG cores are extracted. Eight are delved into further to explain how the visualisation can be used further to drill down to substructure level to understand how the variation in an RG node can be important to a property of interest, right down to the substitution pattern on a ring or the chirality of a group.
