Docking simulations between drugs and HLA molecules associated with idiosyncratic drug toxicity

Idiosyncratic drug toxicities (IDTs) caused by certain drugs are a significant cause of morbidity and mortality for patients. As IDTs are not normally detected even during clinical trials, it is difficult to foresee the risk during the early stage of drug development. Prediction of potential IDTs at the earliest possible opportunity is highly desirable. The strong associations between a particular IDT and a specific human leukocyte antigen (HLA) have been reported and the recent study has disclosed that the direct interaction between a drug in question and the HLA molecule triggers the onset of IDT. Since computational method, especially docking simulation, is applicable to prediction of the binding mode and affinity between the molecules involved in the interaction, it can be used to understand the molecular mechanism of this specific type of drug toxicity. The aim of this review is firstly to outline the methodologies used for docking simulation between drug and HLA molecules. Secondary, an overview of studies on docking simulations between IDT-inducing drugs and the corresponding HLA molecules is given. The results demonstrate that docking simulations are promising to predict the molecular mechanisms of HLA-associated IDTs and point out the causative compounds derived from the relevant drug molecules.