Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes
Yifei Wu,
Tze-chen Hsieh,
Joseph M. Wu,
Xiaoxiao Wang,
Joshua S. Christopher,
Amanda H. Pham,
Justin David-Li Swaby,
Lei Lou,
Zhong-Ru Xie
Affiliations
Yifei Wu
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Tze-chen Hsieh
Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
Joseph M. Wu
Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
Xiaoxiao Wang
Department of Biochemistry & Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
Joshua S. Christopher
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Amanda H. Pham
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Justin David-Li Swaby
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Lei Lou
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Zhong-Ru Xie
Computational Drug Discovery Laboratory, School of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA 30602, USA
Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins.
