Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach

Muhammad Ikhlas Abdjan; Nanik Siti Aminah; Imam Siswanto; Alfinda Novi Kristanti; Yoshiaki Takaya; Muhammad Iqbal Choudhary

doi:10.1039/d1ra02233d

Exploration of stilbenoid trimers as potential inhibitors of sirtuin1 enzyme using a molecular docking and molecular dynamics simulation approach

RSC Adv. 2021 May 27;11(31):19323-19332. doi: 10.1039/d1ra02233d. eCollection 2021 May 24.

Authors

Muhammad Ikhlas Abdjan¹, Nanik Siti Aminah^{1

2}, Imam Siswanto¹, Alfinda Novi Kristanti^{1

2}, Yoshiaki Takaya^{3

4}, Muhammad Iqbal Choudhary^{5

4}

Affiliations

¹ Departement of Chemistry, Faculty of Science and Technology, Universitas Airlangga Surabaya 60115 Indonesia nanik-s-a@fst.unair.ac.id.
² Biotechnology of Tropical Medicinal Plants Research Group, Universitas Airlangga Indonesia.
³ Faculty of Pharmacy, Meijo University 150 Yagotoyama, Tempaku Nagoya 468-8503 Japan.
⁴ Adjunct Professor Department of Chemistry, Faculty of Science and Technology, Universitas Airlangga Komplek Kampus C UNAIR, Jl. Mulyorejo Surabaya Indonesia.
⁵ H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi Karachi-75270 Pakistan.

Abstract

A combination of molecular docking and molecular dynamics simulation (250 ns) has been carried out to study the interaction of stilbenoid trimer compounds with the SIRT1 enzyme as the target protein. SIRT1 expression regulates cellular stress responses that lead to the development of cancer. Redocking showed a good native ligand pose with an RMSD value of 1.40 Å at the receptor active site's coordinates. The molecular docking score uses a grid score functional (kcal mol^-1), which shows results of 1NS: 79.56, TS1: -26.83, TS2: -87.77, and TS3: -83.67. The TS2 and TS3 candidates were chosen for further analysis because they had a lower grid score than the native ligand (1NS). Furthermore, prediction of binding free energy (kcal mol^-1) using the Quantum Mechanics/generalized Born Surface Area (QM/MM-GBSA) method shows the results of 1NS: -31.52 ± 0.39, TS2: -58.99 ± 0.34, and TS3: -43.38 ± 0.35. These results indicate that the TS2 and TS3 compounds have good potential as inhibitors of the SIRT1 enzyme. Additionally, the amino acid residues were responsible for the inhibition mechanism through hydrogen bond interactions at the molecular level, including ASP22, PHE91, PRO11, ILE165, ASP166, and VAL230. The observations made in this study provide theoretical information for exploring the stilbenoid trimers as anticancer agents by targeting the SIRT1 enzyme.