Gilberto Tura Diano
ABSTRACT
The Mas-related G-protein coupled receptor X2 (MRGPRX2) is involved in the immune response and has been implicated in adverse drug reactions such as drug-induced pseudoallergy and anaphylaxis. Conotoxins from the O1 superfamily have been shown to have potent and selective pharmacological activity against various ion channels and more recently, its activity on G protein coupled receptors. This study explores the binding and molecular dynamics of select Conotoxin O1 peptides using computer-aided drug design methods for possible treatment of drug-induced pseudoallergy and associated inflammatory reactions by inhibiting the MRGPRX2. The study uses docking studies and MM/GBSA analysis to evaluate select Conotoxin O1 peptides (natural constructs from Conus spp.) with the MRGPRX2. The aim of this study is to expand the catalogue of possible conopeptides-derived ligand for drug-induced pseudoallergy treatment and provide an in silico framework for using peptide drugs in selectively targeting MRGPRX2.
- ]Adams DJ, Alewood PF, Craik DJ, Drinkwater RD, Lewis RJ. (1999). Conotoxin and their Potential Pharmaceutical Applications. Drug Development Research 46: 219-234Google Scholar
Cross Ref
- J, Braunbeck S, Zaki N, Minniberger S, Chebli M, Plested AJR. (2022). The action of Con-ikot-ikot toxin on single AMPA-type glutamate receptors. Journal of General Physiology: Neuroscience Collection 154(5): e202112912Google ScholarCross Ref
- Barbier J (2004). A δ-Conotoxin from Conus ermineus Venom inhibits inactivation in Vertebrate Neuronal Na+ Channels but not in Skeletal and Cardiac Muscles. Journal of Biological Chemistry 279(6): 4680-4685Google ScholarCross Ref
- Bawazir M, Amponnawarat A, Hui Y, Oskeritzian C, Ali H. (2022). Inhibition of MRGPRX2 but not FcɛRI or MrgprB2-mediated mast cell degranulation by a small molecule inverse receptor agonist. Frontier in Immunology 13: 1033794Google ScholarCross Ref
- Chen F, Liu H, Sun HY, Pan PC, Li YY, Li D, Hou TJ. Assessing the performance of the MM/PBSA and MM/GBSA methods. 6. Capability to predict protein-protein binding free energies and re-rank binding poses generated by protein-protein docking. Physical Chemistry Chemical Physics, 2016, 18(18):22129-22139Google Scholar
- Feng T, Chen F, Kang Y, Sun HY, Liu H, Li D, Zhu F, Hou TJ. HawkRank: a new scoring function for protein-protein docking based on weighted energy terms. Journal of Cheminformatics, 2017, 9(1):66Google Scholar
- Hasan MM, Starobova H, Mueller A, Vetter I, Lewis RJ. (2021). Subcutaneous ω-Conotoxins alleviate mechanical pain in rodent models of Acute Peripheral Neuropathy. Marine Drugs 19(2): 106Google ScholarCross Ref
- Hou TJ, Qiao XB, Zhang W, Xu XJ. Empirical Aqueous Solvation Models Based on Accessible Surface Areas with Implicit Electrostatics. Journal of Physical Chemistry B, 2002, 106(43):11295-11304Google Scholar
- Hou TJ, Wang JM, Li YY, Wang W. Assessing the performance of the MM/PBSA and MM/GBSA methods: I. The accuracy of binding free energy calculations based on molecular dynamics simulations. Journal of Chemical Information & Modeling, 2011, 51(1):69-82Google Scholar
- Jurkovicova-Tarabova B, Lacinova L. (2019). Structure, function and regulation of Cav2.2 N-type calcium channels. General Physiology and Biophysics 38(2): 101-110Google ScholarCross Ref
- Lu A, Yang L, Xu S, Wang C. (2014). Various conotoxin diversification revealed by a venomic study of Conus flavidus. Molecular and Cellular Proteomics 13(1): 105-118Google ScholarCross Ref
- McNeil B. (2021). MRGPRX2 and Adverse Drug Reactions. Frontier in Immunology 12: 676354Google ScholarCross Ref
- Sadeghi M, McArthur JR, Finol-Urdaneta RK, Adams DJ. (2017). Analgesic conopeptides targeting G protein-coupled receptors reduce excitability of sensory neurons. Neuropharmacology 127, 116-123Google ScholarCross Ref
- Sun HY, Li YY, Tian S, Xu L, Hou, TJ. Assessing the performance of MM/PBSA and MM/GBSA methods. 4. Accuracies of MM/PBSA and MM/GBSA methodologies evaluated by various simulation protocols using PDB bind data set. Physical Chemistry Chemical Physics, 2014, [15]</number>Volpon L (2004). NMR solution structure of delta-conotoxin EVIA from Conus ermineus that selectively acts on vertebrate neuronal Na+ channels. The Journal of Biological Chemistry 279(20): 21356-66Google Scholar
- Wang J, Zhang Y, Hu S, Ge S, Jia M, Wang N. (2021). Resveratrol inhibits MRGPRX2-mediated mast cell activation via Nrf2 pathway. International Immunopharmacology 93: 107426Google ScholarCross Ref
- Wang J, Zhang Y, Li C, Ding Y, Hu S, An H. (2020). Inhibitory function of Shikonin on MRGPRX2-mediated pseudo-allergic reactions induced by the secretagogues. Phytomedicine 68: 153149Google ScholarCross Ref
- Wang N (2021). Imperatorin ameliorates mast cell-mediated allergic airway inflammation by inhibiting MRGPRX2 and CamKII/ERK signaling pathway. Biochemical Pharmacology 184: 114401Google ScholarCross Ref
- Weng GQ, Wang EC, Wang Z, Liu H, Li D, Zhu F, Hou TJ. HawkDock: a web server to predict and analyze the structures of protein-protein complexes based on computational docking and MM/GBSA. Nucleic Acids Research, 2019, 47(W1): W322-W330Google Scholar
- Zacharias M. Protein–protein docking with a reduced protein model accounting for side-chain flexibility. Protein Science, 2003, 12(6):1271-1282Google Scholar
- Zamora-BustillosR, Martinez-Nunez MA, Aguilar M, Colli-Dula R, Brito-Dominguez D. (2021). Identification of Novel Conotoxin Precursors from the Cone Snail Conus spurius by High-Throughput RNA Sequencing. Marine Drugs 19(10), 547Google ScholarCross Ref
- NorengS, Li T, Payandeh J. (2021). Structural Pharmacology of Voltage-Gated Sodium Channels. Journal of Molecular Biology 433(17): 166967Google ScholarCross Ref
Index Terms
- In silico Molecular Docking Studies and MM/GBSA Analysis of Select Conotoxin O1 peptides with mas-related G protein coupled receptor X2
Recommendations
In silico 3-D structure prediction and molecular docking studies of inosine monophosphate dehydrogenase from Plasmodium falciparum
Display Omitted Growing resistance in malarial parasites, particularly in Plasmodium falciparum needs for development of novel drug targets.Inosine monophosphate dehydrogenase (IMPDH) is an important target for antimalarial drug discovery.A homology ...
Refinement of G protein-coupled receptor structure models: Improving the prediction of loop conformations and the virtual ligand screening performances
BCB '20: Proceedings of the 11th ACM International Conference on Bioinformatics, Computational Biology and Health InformaticsG protein-coupled receptors (GPCRs) constitute the largest superfamily of membrane proteins. They mediate most of the physiological processes of the human body and form the largest group of potential drug targets. Therefore, knowledge of their three-...
Comments