Induced-Fit Posing (Confined)¶
In hit-to-lead (H2L), where hits from screening are assessed and processed through limited optimization to identify propitious lead compounds, knowing how hits bind to the binding site of the target can offer useful guidance in selecting promising leads. However, predicting the binding pose of hits can be challenging, especially when the hit list contains high chemical diversity, and requires an induced change in the binding site residue sidechains.
Induced-Fit Posing (Confined), a new pose prediction tool for the H2L stage of drug discovery, is a 3-step protocol for the correct prediction of the binding pose of a ligand which requires induced-fit of receptor binding site residue sidechains. (We refer to the induced-fit process as confined due to its limited scope.)