Informatics in Medicine Unlocked (Jan 2022)
Molecular docking analysis of H1 and H2 antihistamines groups with l-asparaginase II for reducing allergenicity; an in silico approach
Abstract
Introduction: Cancer is a pervasive disease with different types spreading widely worldwide. Acute lymphoblastic leukemia (ALL) is the bone marrow lymphocyte cancer related to the malignancy of B or T lymphoblast white blood cells. This disease has a rapid progression and can be fatal within several months without treatment. The use of l-asparaginase II is the most important treatment with specific side effects that can provoke allergic reactions, such as anaphylaxis. The purpose of this study was to evaluate the possibility of using l-asparaginase II and antihistamine without the antihistamine interfering with the l-asparaginase II ligand. Methods: The UniProt and RCSB PDB databases were used to access ansB gene and l-asparaginase crystallographic structure information. Allergome, Allermatch, and SDAP databases were used to examine epitope's allergenicity and predict protein allergenicity. Using DrugBank and ChEMBL, 47H1 and 8H2 approved antihistamines were achieved. The 3D structures were obtained from the PubChem database. Also, molecular docking analysis was performed in the Molegro 6.0 software. Results: The primary epitope responsible for the allergenicity of the l-asparaginase II enzyme with two possible areas of allergenic was introduced. The results showed that among all H1 and H2 antihistamines, Betazole (−64.0225 kcal/mol) had a better binding affinity than other antihistamines to the l-asparaginase II enzyme (−64.5873 kcal/mol). Other antihistamines may interfere with l-asparaginase 2-asparagine activity. Conclusion: It can be stated that drugs with higher binding affinity than asparagine can have a negative effect on l-asparaginase II enzyme function. Betazole was identified as a suitable drug for allergy control with an appropriate binding affinity to asparagine, and therefore, it can have a minimal drug interaction with the l-asparaginase II enzyme.
