Molecular docking and dynamics simulation of piperine as a potential inhibitor of class C beta-lactamase

Main Article Content

Sayed Hussain Mosawi
Hamza Mansoori
Abdul Musawer Bayan
Najmeh Fani


Background: Antimicrobial resistance is a major concern of human being through the decades which are the cause of hundred thousand of death. β -lactamases secretion by bacteria is one of main resistant mechanism enzymes bacteria to fight antibiotics. Multiple investigation has performed to inhibit the β-lactamase enzyme activity which is one of the important ways to reduce microbial drug resistance and increase the effectiveness of antibiotics.

Methods: Molecular docking was performed to determine the binding pose and binding energy of class C beta lactamase with piperine using Autodock 4.2.2 software. Molecular dynamic simulation was carried out for enzyme utilizing GROMACS 2019.6 program applying AMBER99SB force field.

Results: Molecular docking results and interaction analysis of molecular dynamics simulations showed favorable hydrogen bonds and van der Waals interactions of Piperine with AmpC. The results of this paper may provide a new perspective to solve the problem of drug resistance caused by bacteria and help to design new beta-lactamase inhibitors in the future.

Conclusion: By using the valuable techniques of molecular docking and molecular dynamics simulation, this paper suggests that Piperine, which is the main component of black pepper and has significant medicinal effects, can be used to inhibit AmpC β -lactamase class C enzyme.

Article Details

How to Cite
Mosawi, S. H., Mansoori, H., Bayan , A. M., & Fani, N. (2023). Molecular docking and dynamics simulation of piperine as a potential inhibitor of class C beta-lactamase . Afghanistan Journal of Infectious Diseases, 1(1), 27–32.
Research Article
Author Biographies

Sayed Hussain Mosawi, Ghalib University

Medical Sciences Research Center, Ghalib University, Kabul, Afghanistan.

Hamza Mansoori, Ghalib University

Medical Sciences Research Center, Ghalib University, Kabul, Afghanistan.

Abdul Musawer Bayan , Ghalib University

Medical Sciences Research Center, Ghalib University, Kabul, Afghanistan.

Najmeh Fani, Iliya Computational Research Center (ICRC)

Iliya Computational Research Center (ICRC), Research & Development Centre, Isfahan, 8159693251, Iran


Fleming A. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Bulletin of the World Health Organization. 2001; 79:780-90.

Scholar EM, Scholar EM, Pratt WB. The antimicrobial drugs: Oxford University Press, USA; 2000.

Giwercman B, Jensen ET, Høiby N, Kharazmi A, Costerton JW. Induction of beta-lactamase production in Pseudomonas aeruginosa biofilm. Antimicrobial agents and chemotherapy. 1991; 35(5):1008-10.

González-Bello Cn, Rodríguez D, Pernas M, Rodriguez A, Colchón E. β-Lactamase inhibitors to restore the efficacy of antibiotics against superbugs. Journal of medicinal chemistry. 2019;63(5):1859-81.

Hall BG, Barlow M. Revised Ambler classification of β-lactamases. Journal of Antimicrobial Chemotherapy. 2005; 55(6):1050-1.

Donowitz GR, Mandell GL. Beta-lactam antibiotics. New England Journal of Medicine. 1988; 318(7):419-26.

Webb GF, D'Agata EM, Magal P, Ruan S. A model of antibiotic-resistant bacterial epidemics in hospitals. Proceedings of the National Academy of Sciences. 2005; 102(37):13343-8.

Ng TM, Khong WX, Harris PN, De PP, Chow A, Tambyah PA, et al. Empiric piperacillin-tazobactam versus carbapenems in the treatment of bacteraemia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae. PloS one. 2016; 11(4):e0153696.

Rafailidis PI, Ioannidou EN, Falagas ME. Ampicillin/sulbactam. Drugs. 2007;67(13):1829-49.

Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. Journal of natural products. 2016; 79(3):629-61.

Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nature reviews Drug discovery. 2005;4 (3):206-20.

Haq IU, Imran M, Nadeem M, Tufail T, Gondal TA, Mubarak MS. Piperine: A review of its biological effects. Phytotherapy Research. 2021;35(2):680-700.

Okwute SK, Egharevba HO. Piperine-type amides: review of the chemical and biological characteristics. International Journal of Chemistry. 2013;5(3):99.

Li Y, Gao L, Shi H, Feng S, Tian X, Kong L, et al. Piperine inhibits the transformation of endothelial cells into fibroblasts. Zhonghua xin xue Guan Bing za zhi. 2019; 47(7):554-60.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic acids research. 2000; 28(1):235-42.

Sterling T, Irwin JJ. ZINC 15–ligand discovery for everyone. Journal of chemical information and modeling. 2015; 55(11):2324-37.

Chen Y, Shoichet BK. Molecular docking and ligand specificity in fragment-based inhibitor discovery. Nature chemical biology. 2009; 5(5):358-64.

Olsen L, Pettersson I, Hemmingsen L, Adolph H-W, Jørgensen FS. Docking and scoring of metallo-β-lactamases inhibitors. Journal of computer-aided molecular design. 2004; 18(4):287-302.

Sousa da Silva AW, Vranken WF. ACPYPE-Antechamber python parser interface. BMC research notes. 2012; 5:1-8.

Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJ. GROMACS: fast, flexible, and free. Journal of computational chemistry. 2005; 26 (16):1701-18.