IN SILICO MOLECULAR MODELING AND DOCKING STUDIES OF HERBAL COMPOUND MEDIATED INHIBITION OF Κβ KINASEβ (INHIBITOR OF Κβ KINASE SUBUNIT β) FOR OSTEOARTHRITIS TREATMENT
DOI:
https://doi.org/10.22159/ajpcr.2018.v11i4.24128Keywords:
Docking studies, Nil, Herbal medicine, Osteoarthritis, NilAbstract
  Objective: This study was intended to investigate and characterize the phytoconstituents of plant herbs and inhibitors, evaluate its anti-osteoarthritis (OA) and anti-inflammatory potential under in silico conditions.
Methods: Docking studies were performed to find out the maximum interaction between design ligands and selected five proteins using Schrodinger Software NY. Structures of selected proteins were downloaded from protein data bank.
Results: Morin, salubrinal, icariin, and chondroitin sulfate, and sesamol have higher binding energy than other compounds. Based on these properties out of 9 compounds we have selected 5 best-docked and compounds selected were molecular dynamics simulation with inhibitor of κβ kinase subunit (IKK) β. Arg20, Leu21, Thr23, Lys44, Glu61, Glu97, Cys99, Lys106, Asp145, Asn150, andAsp166 were actively involved in H-bond interaction with ligands. Each compound has different binding modes, which reflects the difference of interacting residues with different functional groups. Morin has better interaction than other compounds. Either Cys99 or Lys44 found predominantly in most of the complex except in β-ecdysterone whereas both found interacting with morin.
Conclusion: The results revealed out that the herbal compounds can inhibit the IKKβ protein. The virtual screening yielded five potential IKKβ inhibitors: Morin, salubrinal, icariin, and chondroitin sulfate, and sesamol. This inhibitor shows good interaction, energy, and pharmacophoric activity and will be suitable for further experiments of an anti-OA target.
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References
Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone 2012;51:249-57.
Ulivi V, Giannoni P, Gentili C, Cancedda R, Descalzi F. P38/NF-B-dependent expression of COX-2 during differentiation and inflammatory response of chondrocytes. J Cell Biochem 2008;104:1393-406.
Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB. NF-kappaB signaling: Multiple angles to target OA. Curr Drug Targets 2010;11:599-613.
Marcu KB, Otero M, Olivotto E, Borzi RM, Goldring MB. NF-kappaB signaling: Multiple angles to target OA. Curr Drug Targets 2010;11:599-613.
Mariani E, Pulsatelli L, Facchini A. Signaling pathways in cartilage repair. Int J Mol Sci 2014;15:8667-98.
Paul S, Das AP, Bhattacharjee S. Rheumatoid arthritis: Molecular basis and cures from nature. Int J Pharm Pharm Sci 2015;7:30-9.
Chabib L, Awaluddin R, Ikawati Z, Martien R, Ismail H. Molecular docking, pharmacophore modelling, and adme-toxicity prediction of curcumin analog compounds as inflammatory inhibitor on rheumatoid arthritis. Int J Pharm Pharm Sci 2017;9:16-21.
Chen WP, Wang YL, Tang JL, Hu PF, Bao JP, Wu LD. Morin inhibits interleukin-1β-induced nitric oxide and prostaglandin E 2 production in human chondrocytes. Int Immunopharmacol 2012;12:447-52.
Hamamura K, Lin CC, Yokota H. Salubrinal reduces expression and activity of MMP13 in chondrocytes. Osteoarthritis Cartilage 2013;21:764-72.
Zeng L, Wang W, Rong XF, Zhong Y, Jia P, Zhou GQ, et al. Chondroprotective effects and multi-target mechanisms of Icariin in IL-1 beta-induced human SW 1353 chondrosarcoma cells and a rat osteoarthritis model. Int Immunopharmacol 2014;18:175-81.
Stabler TV, Huang Z, Montell E, Vergés J, Kraus VB. Chondroitin sulphate inhibits NF-κB activity induced by interaction of pathogenic and damage associated molecules. Osteoarthritis Cartilage 2017;25:166-74.
Lu YC, Jayakumar T, Duann YF, Chou YC, Hsieh CY, Yu SY, et al. Chondroprotective role of sesamol by inhibiting MMPs expression via retaining NF-κB signaling in activated SW1353 cells. J Agric Food Chem 2011;59:4969-78.
Haseeb A, Chen D, Haqqi TM. Delphinidin inhibits IL-1β- induced activation of NF-κB by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes. Rheumatology 2013;52:998-1008.
Wang JH, Shih KS, Wu YW, Wang AW, Yang CR. Histone deacetylase inhibitors increase microRNA-146a expression and enhance negative regulation of interleukin-1β signaling in osteoarthritis fibroblast-like synoviocytes. Osteoarthritis Cartilage 2013;21:1987-96.
Wang D, Qiao J, Zhao X, Chen T, Guan D. Thymoquinone inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by suppressing NF-κB and MAPKs signaling pathway. Inflammation 2015;38:2235-41.
Zhang X, Xu X, Xu T, Qin S. β-Ecdysterone suppresses interleukin-1β- induced apoptosis and inflammation in rat chondrocytes via inhibition of NF-κB signaling pathway. Drug Dev Res 2014;75:195-201.
Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, et al. Crystal structure of a human IκB kinase β asymmetric dimer. J Biol Chem 2013;288:22758-67.
Schrödinger, LLC. Schrödinger Release 2015-3: Maestro, version 10.3. New York, NY: Schrödinger, LLC; 2015.
Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: A new approach for rapid, accurate docking and scoring 1. Method and assessment of docking accuracy. J Med Chem 2004;47:1739-49.
Singh N, Warshel A. Absolute binding free energy calculations: On the accuracy of computational scoring of protein-ligand interactions. Proteins 2010;78:1705-23.
Lyne PD, Lamb ML, Saeh JC. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem 2006;49:4805-8.
Schrödinger, LLC. Schrödinger Release 2015-3: Prime, Version 4.1. New York, NY: Schrödinger, LLC; 2015.
Reddy KK, Singh SK, Tripathi SK, Selvaraj C, Suryanarayanan V. Shape and pharmacophore-based virtual screening to identify potential cytochrome P450 sterol 14α-demethylase inhibitors. J Rec Signal Transduct 2013;33:234-43.
Lyne PD, Lamb ML, Saeh JC. Accurate prediction of the relative potencies of members of a series of kinase inhibitors using molecular docking and MM-GBSA scoring. J Med Chem 2006;49:4805-8.
Ponder JW, Case DA. Force fields for protein simulations. Adv Protein Chem 2003;66:27-85.
Veeramachaneni GK, Raj KK, Bondili JS, Talluri VR. Screening and molecular docking studies of new natural agonists against peroxisome proliferator-activated receptor-alpha targeted to treat obesity. Asian J Pharm Clin Res 2016;9:80-4.
Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, et al. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 2006;49:6177-96.
Gurula H, Loganathan T, Vashum Y, Pannerselvam S, Vetrivel U, Samuel S. In Silico screening of potent ppargamma agonists among natural anticancer compounds of indian origin. Asian J Pharm Clin Res 2016;9:320-4.
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