Molecular Docking to Identify Associations Between Drugs and Class I Human Leukocyte Antigens for Predicting Idiosyncratic Drug Reactions
2015
Idiosyncratic drug reactions (IDRs) are rare, somewhat dose-independent, patient-specific and hard to predict. Human
leukocyte antigens (HLAs) are the major histocompatibility complex (MHC) in humans, are highly polymorphic and are
associated with specific IDRs. Therefore, it is important to identify potential drug-HLA associations so that individuals who
would develop IDRs can be identified before drug exposure. We harvested the associations between drugs and class I HLAs
from the literature. The results revealed that there are many drug-HLA pairs without clinical data. For better potential interactions
of the drug-HLA pairs, molecular docking was used to explore the potential of associations between the drugs and HLAs. From
the analysis of docking scores between the 17 drugs and 74 class I HLAs, it was observed that the known significantly associated
drug-HLA pairs had statistically lower docking scores than those not reported to be significantly associated (t-test p < 0.05). This
indicates that molecular docking could be utilized for screening drug-HLA interactions and predicting potential IDRs. Examining
the binding modes of drugs in the docked HLAs suggested several distinct binding sites inside class I HLAs, expanding our
knowledge of the underlying interaction mechanisms between drugs and HLAs.
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