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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Novel Monoclonal Antibodies for the Treatment of Chronic Lymphocytic Leukemia
Current Cancer Drug Targets Harnessing the Tumor Suppressor Function of FOXO as an Alternative Therapeutic Approach in Cancer
Current Drug Targets Flavonoids in Atherosclerosis: An Overview of Their Mechanisms of Action
Current Medicinal Chemistry Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment
Current Vascular Pharmacology Editorial [Hot Topic:Cell Metabolism as Therapeutic Target in Human Disease (Executive Guest Editors: Walter Malorni and Rosa Vona)]
Current Pharmaceutical Design The Influence of Ionizing Radiation on Exosome Composition, Secretion and Intercellular Communication
Protein & Peptide Letters Extracellular Signals for Guiding Mesenchymal Stem Cells Osteogenic Fate
Current Stem Cell Research & Therapy MICA Molecules in Disease and Transplantation, a Double-Edged Sword?
Current Immunology Reviews (Discontinued) Cancer-related Fatigue, Inflammation and Thyrotropin-releasing Hormone
Current Aging Science Therapeutic Approaches Targeting Pathological Tau Aggregates
Current Pharmaceutical Design Fluoride Effects: The Two Faces of Janus
Current Medicinal Chemistry Voltage-Gated Sodium Channels as Therapeutic Targets for Treatment of Painful Diabetic Neuropathy
Mini-Reviews in Medicinal Chemistry Receptor Tyrosine Kinases are Signaling Intermediates of G Protein- Coupled Receptors
Current Pharmaceutical Design Role of Antimicrobial Peptides Expressed by Host Cells Upon Infection by Helicobacter pylori
Protein & Peptide Letters Expression Profiling of Estrogen Responsive Genes Using Genomic and Proteomic Techniques for the Evaluation of Endocrine Disruptors
Current Pharmacogenomics Pro-Inflammatory Cytokines and their Actions on the Metabolic Disturbances Associated with Cancer: Implications in Cachexia
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Interaction Network of MicroRNAs with Cytokines and Signaling Pathways in Allergic Asthma
MicroRNA Polysaccharide-K (PSK) in Cancer - Old Story, New Possibilities?
Current Medicinal Chemistry Current Therapeutic Advances in Patients and Experimental Models of Huntington's Disease
Current Drug Targets Serum Amyloid A and Its Potential Physiological / Pathological Functions - an Overview of Patents
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery