Identify on-target and off-target drug-protein interactions

Clozapine is one of the multi-target drugs that remains the only approved treatment for treatment-resistant schizophrenia. The multi-target nature of second-generation drugs unsurprisingly leads to off-target interactions, causing adverse drug reactions. Identifying drug-protein interactions and distinguishing them as on-target or off-target remains a high priority to minimise adverse drug reactions and discover new antipsychotic drugs. We intend to identify and characterise these drug-protein interactions of widely prescribed antipsychotics using advanced computational drug discovery approaches. Novel AI applications such as AlphaFold can now predict the 3D protein structures with very high accuracy, perhaps shortening the time from novel ideas to medical intervention. What used to be a lengthy, onerous and uncertain path to obtain the 3D structures of protein targets for drug discovery can now be reduced markedly, producing new opportunities to accelerate drug discovery. There are two main directions to drug discovery. 1. We will use inverse virtual screening where a drug molecule is docked into a collection of proteins, enabling the prediction of drug side effects and toxicity. 2. We will use a conventional virtual screening approach where a protein is docked into a collection of drug molecules to discover new drugs.