Artificial Intelligence Teaches Drugs to Target Proteins by Tackling the Induced Folding Problem

We explore the possibility of a deep learning (DL) platform that steers drug design to target proteins by inducing binding-competent conformations. We deal with the fact that target proteins are usually not fixed targets but structurally adapt to the ligand in ways that need to be predicted to enable pharmaceutical discovery. In contrast with protein folding predictors, the proposed DL system integrates signals for structural disorder to predict conformations in floppy regions of the target protein that rely on associations with the purposely designed drug to maintain their structural integrity. This is tantamount to solve the drug-induced folding problem within an AI-empowered drug discovery platform. Preliminary testing of the proposed DL platform reveals that it is possible to infer the induced folding ensemble from which a therapeutically targetable conformation gets selected by DL-instructed drug design.