Molecular Dynamic Simulation of Asiatic Acid Derivatives Complex With Inducible Nitric Oxide Synthase Enzyme as an Anti-Inflammatory

Abstract

Objective: The aim of this study was to determine the stability interaction of asiatic acid derivatives (AA) complex with inducible nitric oxide synthase (iNOS) enzyme as an anti-inflammatory using Molecular Dynamic (MD) simulation.
 Methods: The methods were consisting of validation of molecular docking, molecular docking to calculate binding affinity within the complex between the compounds and iNOS enzyme by using MMGBSA (Molecular Mechanics/Generalized Born Surface Area), and MD system preparation, MD production as well as MD analysis using AMBER18.
 Results: The result of validation and molecular docking were AA5 has the most negative Gibbs energy that is -9.17 kcal/mol, which has better binding affinity than other derivatives than other derivatives. The molecular dynamics simulation of the modified structure of asiatic acid showed that binding energy value and RMSD of AA5, AA6 and AA9 have a lower value compared to arginine as a substrate of iNOS enzyme. Molecular Dynamics that have been occurred to the best three compounds chosen shown good result in terms of stability after 100 ns length simulation. And the lowest binding affinity has been achieved by a compound called AA5. Out of all ligands that have been simulated shown that their binding affinity was lower than AA5 that reached-44.6753 kcal/mol.
 Conclusion: This studies conclude that AA5 considerably more potential as a selective inhibitor of iNOS enzyme as an anti-inflammatory.

Stability Analysis of the Asiatic Acid-COX-2 Complex Using 100 ns Molecular Dynamic Simulations and Its Selectivity against COX-2 as a Potential Anti-Inflammatory Candidate

“…Therefore, the stability of the bond between the ligand and receptor becomes stronger. The existence of fluctuations in the amino acid residues allows the ligand to bind to the active site of the COX-2 enzyme [20]. The COX-2 active site is divided into three important regions; the first hydrophobic pockets are Tyr385, Trp387, Phe518, Ala201, Tyr248, and Leu352; the second region is the entrance of the active site coated by hydrophilic residues Arg120, Glu524, Tyr355; and the third is a side pocket coated by His90, Arg513, and Val523 [21].…”

SIMULASI IN SILICO SENYAWA AKTIF DAUN JAMBU MAWAR (Syzygium jambos L. Alston) SEBAGAI OBAT ANTIINFLAMASI

“…Makromolekul yang dipilih adalah 1NSI merupakan struktur dari enzim iNOS dengan resolusi 2,55 Å dan 3EWJ yang merupakan struktur dari reseptor TNF-α dengan resolusi 1,80 Å. Makromolekul tersebut diperoleh dari hasil difraksi sinar-X. Masing-masing struktur makromolekul tersebut memenuhi syarat maksimum resolusi yaitu sebesar 3,0Å [10].…”

“…Interaksi ikatan yang dinyatakan memenuhi kriteria penambatan molekul adalah ikatan hidrogen yang dapat menunjukkan afinitas suatu molekul terhadap protein target yang membentuk interaksi elektrostatik (donor dan akseptor hidrogen) [13]. Berdasarkan penelitian yang telah dilakukan oleh Ida Musfiroh pada tahun 2013 menjelaskan bahwa asam amino yang berperan dalam ikatan iNOS dengan L-Arginine yaitu ikatan hidrogen diantaranya tyrosin, asam aspartat, asam glutamat dan glutamin [10]. Interaksi dapat dilihat dari nilai energi bebas dan konstanta inhibisi yang rendah [16].…”

An Overview of Epigenetic Drugs, and Their Virtual Screening Study Retrieved From Zinc Database Along With an Autodock Study of the Best Inhibitor

“…In the pharmaceutical research field, we now come up with various types of docking and virtual screening research works such as understanding of structural interactions of protein and ligand [60], drug design and discovery [61], and docking against phytochemical screening, which all contribute to the enhancements of not only the pharmaceutical research productivity but also academic authenticity [62,63,64]. I am glad to see that this work is one of them and I wish this type of docking and virtual screening research would continue to be prosperous and productive in the pharmaceutical sciences.…”