Next Article in Journal
Volatilomic Analysis of Four Edible Flowers from Agastache Genus
Previous Article in Journal
Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses
Previous Article in Special Issue
New Molecular Insights into the Inhibition of Dipeptidyl Peptidase-4 by Natural Cyclic Peptide Oxytocin
Open AccessArticle

Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation

1
School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China
2
Xinxiang Key Laboratory of Biomedical Information Research, Xinxiang 453003, China
3
Henan Engineering Laboratory of Combinatorial Technique for Clinical and Biomedical Big Data, Xinxiang 453003, China
4
School of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China
5
State Key Laboratory of Precision Spectroscopy, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China
6
Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, Co-Innovation Center of Henan Province for New Drug R & D and Preclinical Safety, Institute of Drug Discovery and Development, School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China
7
College of Sanquan, Xinxiang Medical University, Xinxiang 453003, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Florenci V. González
Molecules 2019, 24(24), 4479; https://doi.org/10.3390/molecules24244479
Received: 10 October 2019 / Revised: 28 November 2019 / Accepted: 3 December 2019 / Published: 6 December 2019
(This article belongs to the Special Issue Design and Synthesis of Protease Inhibitors)
Overexpression of lysine specific demethylase 1 (LSD1) has been found in many cancers. New anticancer drugs targeting LSD1 have been designed. The research on irreversible LSD1 inhibitors has entered the clinical stage, while the research on reversible LSD1 inhibitors has progressed slowly so far. In this study, 41 stilbene derivatives were studied as reversible inhibitors by three-dimensional quantitative structure–activity relationship (3D-QSAR). Comparative molecular field analysis (CoMFA q 2 = 0.623, r 2 = 0.987, r pred 2 = 0.857) and comparative molecular similarity indices analysis (CoMSIA q 2 = 0.728, r 2 = 0.960, r pred 2 = 0.899) were used to establish the model, and the structure–activity relationship of the compounds was explained by the contour maps. The binding site was predicted by two different kinds of software, and the binding modes of the compounds were further explored. A series of key amino acids Val288, Ser289, Gly314, Thr624, Lys661 were found to play a key role in the activity of the compounds. Molecular dynamics (MD) simulations were carried out for compounds 04, 17, 21, and 35, which had different activities. The reasons for the activity differences were explained by the interaction between compounds and LSD1. The binding free energy was calculated by molecular mechanics generalized Born surface area (MM/GBSA). We hope that this research will provide valuable information for the design of new reversible LSD1 inhibitors in the future. View Full-Text
Keywords: LSD1; molecular inhibitors; stilbene derivatives; molecular docking; 3D-QSAR; molecular dynamics simulations LSD1; molecular inhibitors; stilbene derivatives; molecular docking; 3D-QSAR; molecular dynamics simulations
Show Figures

Graphical abstract

MDPI and ACS Style

Xu, Y.; He, Z.; Yang, M.; Gao, Y.; Jin, L.; Wang, M.; Zheng, Y.; Lu, X.; Zhang, S.; Wang, C.; Zhao, Z.; Zhao, J.; Gao, Q.; Duan, Y. Investigating the Binding Mode of Reversible LSD1 Inhibitors Derived from Stilbene Derivatives by 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulation. Molecules 2019, 24, 4479.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop