In-Silico Study of N-Hydroxysuccinimide Folate and GAPDH as Targeting Agents for Tuberculosis Treatment

Laurentius Ivan Ageng Marhaendra; Muchtaridi Muchtaridi; Yudi Rosandi; Amirah Mohd Gazzali

doi:10.24198/ijpst.v12s2.59597

In-Silico Study of N-Hydroxysuccinimide Folate and GAPDH as Targeting Agents for Tuberculosis Treatment

Laurentius Ivan Ageng Marhaendra, Muchtaridi Muchtaridi, Yudi Rosandi, Amirah Mohd Gazzali

Abstrak

Tuberculosis remains a major public health concern due to emerging cases of drug resistance. To overcome this issue, the effectiveness of antitubercular medications must be reinforced. One of the methods that can be used is using active targeting, which involves small molecules that bind to a specific receptor. In this research, we study the potential of N-hydroxysuccinimide (NHS) folate to be used as the targeting agent against the GAPDH (glyceraldehyde-3-phosphate dehydrogenase) cell-surface receptor, a common virulence factor found on many pathogenic bacteria, including Mycobacterium tuberculosis. We conducted this research using computational methods, specifically molecular docking and molecular dynamics simulation. Based on the evaluation of molecular docking and molecular dynamics simulation results, NHS-folate is predicted to have a huge potential to be an active targeting agent against the GAPDH receptor of Mycobacterium tuberculosis.

Kata Kunci

antitubercular medications; molecular docking; molecular dynamics simulation; glyceraldehyde-3-phosphate dehydrogenase; N-hydroxysuccinimide folate.

Teks Lengkap:

PDF (English)

Referensi

WHO. Global tuberculosis report 2022 [accessed 1 June 2023]. Available from: https://www.who.int/publications/i/item/9789240061729.

Jankute M, Cox JAG, Harrison J, Besra GS. Assembly of the mycobacterial cell wall. Annu Rev Microbiol. 2015;69(1):405-23.

Walker D, Stevens W. The economics of TB control in developing countries. Expert Opin Pharmacother. 2003;4(3):359-68.

Miller R, Goodman C. Quality of tuberculosis care by pharmacies in low- and middle-income countries: Gaps and opportunities. J Clin Tuberc Mycobact Dis. 2020;18:100135.

Chakaya JM, Menzies R, Steingart K, Hopewell P, Nunn A, Philips H. Treatment of tuberculosis guidelines. 4th ed. Geneva: World Health Organization; 2010.

Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens. Nat Rev Drug Discov. 2013;12(5):388-404.

Manish G, Vimukta S. Targeted drug delivery system: a review. Res J Chem Sci. 2011;1(2):135-8.

Bareford L, Swaan P. Endocytic mechanisms for targeted drug delivery. Adv Drug Deliv Rev. 2007;59(8):748-58.

Danhier F, Feron O, Préat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Controlled Release. 2010;148(2):135-46.

Malhotra H, Patidar A, Boradia VM, Kumar R, Nimbalkar RD, Kumar A, et al. Mycobacterium tuberculosis glyceraldehyde-3-phosphate dehydrogenase (GAPDH) functions as a receptor for human lactoferrin. Front Cell Infect Microbiol. 2017;7:245.

Boradia VM, Malhotra H, Thakkar JS, Tillu VA, Vuppala B, Patil P, et al. Mycobacterium tuberculosis acquires iron by cell-surface sequestration and internalization of human holo-transferrin. Nat Commun. 2014;5(1):4730.

Noh MAA, Rahiman SSF, Wahab HA, Gazzali AM. Discovery of new targeting agents against GAPDH receptor for antituberculosis drug delivery. J Basic Clin Physiol Pharmacol. 2021;32(4):715-22.

Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-61.

Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: new docking methods, expanded force field, and Python bindings. J Chem Inf Model. 2021;61(8):3891-8.

Jiménez J, Doerr S, Martínez-Rosell G, Rose AS, De Fabritiis G. DeepSite: protein-binding site predictor using 3D-convolutional neural networks. Bioinformatics. 2017;33(19):3036-42.

Nnyigide OS, Nnyigide TO, Lee SG, Hyun K. Protein repair and analysis server: A Web server to repair PDB structures, add missing heavy atoms and hydrogen atoms, and assign secondary structures by amide interactions. J Chem Inf Model. 2022;62(17):4232-46.

Hanwell MD, Curtis DE, Lonie DC, Vandermeersch T, Zurek E, Hutchison GR. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J Cheminformatics. 2012;4(1):17.

Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC. GROMACS: fast, flexible, and free. J Comput Chem. 2005;26(16):1701-18.

Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, De Groot BL, et al. CHARMM36: an improved force field for folded and intrinsically disordered proteins. Biophys J. 2017;112(3):175a-6a.

Valdés-Tresanco MS, Valdés-Tresanco ME, Valiente PA, Moreno E. gmx_MMPBSA: a new tool to perform end-state free energy calculations with GROMACS. J Chem Theory Comput. 2021;17(10):6281-91.

Miller BR, McGee TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE. MMPBSA.py: an efficient program for end-state free energy calculations. J Chem Theory Comput. 2012;8(9):3314-21.

DOI: https://doi.org/10.24198/ijpst.v12s2.59597