Abstract
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.
Keywords: Adverse drug reaction, docking, personalized medicine, human leukocyte antigen, idiosyncratic drug reaction, modelling.
Combinatorial Chemistry & High Throughput Screening
Title:Molecular Docking to Identify Associations Between Drugs and Class I Human Leukocyte Antigens for Predicting Idiosyncratic Drug Reactions
Volume: 18 Issue: 3
Author(s): Heng Luo, Tingting Du, Peng Zhou, Lun Yang, Hu Mei, Huiwen Ng, Wenqian Zhang, Mao Shu, Weida Tong, Leming Shi, Donna L. Mendrick and Huixiao Hong
Affiliation:
Keywords: Adverse drug reaction, docking, personalized medicine, human leukocyte antigen, idiosyncratic drug reaction, modelling.
Abstract: 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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Cite this article as:
Luo Heng, Du Tingting, Zhou Peng, Yang Lun, Mei Hu, Ng Huiwen, Zhang Wenqian, Shu Mao, Tong Weida, Shi Leming, L. Mendrick Donna and Hong Huixiao, Molecular Docking to Identify Associations Between Drugs and Class I Human Leukocyte Antigens for Predicting Idiosyncratic Drug Reactions, Combinatorial Chemistry & High Throughput Screening 2015; 18 (3) . https://dx.doi.org/10.2174/1386207318666150305144015
DOI https://dx.doi.org/10.2174/1386207318666150305144015 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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