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. 2023 Jul 12:14:1144632.
doi: 10.3389/fphar.2023.1144632. eCollection 2023.

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening

Somayye Taghvaei  1 , Alireza Taghvaei  2 , Mohammad Saberi Anvar  3 , Chun Guo  4 , Farzaneh Sabouni  1 , Zarrin Minuchehr  3
Affiliations

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening

Somayye Taghvaei et al. Front Pharmacol. .

Abstract

Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative, antiangiogenic, antiproliferative, and pro-apoptotic properties. Methods: In this study, we investigated the interaction of some natural compounds with SENP1 to inhibit its activity. We also screened the ZINC database including natural compounds. Molecular docking was performed, and toxicity of compounds was determined; then, molecular dynamics simulation (MDS) and essential dynamics (ED) were performed on natural compounds with higher free binding energies and minimal side effects. By searching in a large library, virtual screening of the ZINC database was performed using LibDock and CDOCKER, and the final top 20 compounds were allowed for docking against SENP1. According to the docking study, the top three leading molecules were selected and further analyzed by MDS and ED. Results: The results suggest that resveratrol (from the selected compounds) and ZINC33916875 (from the ZINC database) could be more promising SENP1 inhibitory ligands. Discussion: Because these compounds can inhibit SENP1 activity, then they can be novel candidates for cancer treatment. However, wet laboratory experiments are needed to validate their efficacy as SENP1 inhibitors.

Keywords: SENP1; ZINC database; cancer; molecular docking; molecular dynamics simulation; natural compounds; resveratrol.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart of research stes: (A) molecular docking and molecular dynamics of suggested compounds and (B) virtual screening of the ZINC library with 84,000 compounds.
FIGURE 2
FIGURE 2
RMSD, RMSF, Rg, SASA, and intramolecular hydrogen bond plots of free-SENP1 and SENP1 complexes, (black) free-SENP1, (red) aspirin, (green) berberine, (blue) cinnamic acid, (yellow) ferulic acid, (brown) resveratrol, and (gray) momordin.
FIGURE 3
FIGURE 3
Intermolecular hydrogen bonds: (A) aspirin, (B) berberine, (C) cinnamic acid, (D) ferulic acid, (E) resveratrol, and (F) momordin, and (G) distance plots of SENP1 complexes, (black) free-SENP1, (red) aspirin, (green) berberine, (blue) cinnamic acid, (yellow) ferulic acid, (brown) resveratrol, and (gray) momordin.
FIGURE 4
FIGURE 4
Secondary structure plots of compounds: (A) aspirin, (B) berberine, (C) cinnamic acid, (D) ferulic acid, (E) resveratrol, (F) momordin, and (G) free-SENP1.
FIGURE 5
FIGURE 5
Interactions between (A) aspirin, (B) berberine, (C) cinnamic acid, (D) ferulic acid, (E) resveratrol, and (F) momordin individually with SENP1 (2D structures) in molecular docking by Discovery Studio.
FIGURE 6
FIGURE 6
Interactions between (A) aspirin, (B) berberine, (C) cinnamic acid, (D) ferulic acid, (E) resveratrol, and (F) momordin individually with SENP1 by Discovery Studio after molecular dynamics simulation (2D structures).
FIGURE 7
FIGURE 7
Principal component analysis. Projection of the motion for compounds: (black) free-SENP1, (red) aspirin, (green) berberine, (blue) cinnamic acid, (yellow) ferulic acid, (brown) resveratrol, and (gray) momordin.
FIGURE 8
FIGURE 8
Interactions between (A) ZINC79204151, (B) ZINC33916875, (C) ZINC85902334, and (D) momordin individually with SENP1 (2D structures) in molecular docking by Discovery Studio.
FIGURE 9
FIGURE 9
RMSD, RMSF, Rg, SASA, and intramolecular hydrogen bond plots of free-SENP1 and SENP1 complexes (black) free-SENP1, (red) ZINC79204151, (green) ZINC33916875, (blue) ZINC85902334, and (yellow) momordin.
FIGURE 10
FIGURE 10
(A) ZINC79204151, (B) ZINC33916875, (C) ZINC85902334, and (D) momordin (intermolecular hydrogen bonds). (E) Distance plots of SENP1 complexes, (black) ZINC79204151, (red) ZINC33916875, (green) ZINC85902334, and (blue) momordin.
FIGURE 11
FIGURE 11
Secondary structure plots of compounds (A) ZINC79204151, (B) ZINC33916875, (C) ZINC85902334, (D) momordin, and (E) free-SENP1.
FIGURE 12
FIGURE 12
Interactions between (A) ZINC79204151, (B) ZINC33916875, (C) ZINC85902334, and (D) momordin with SENP1 by Discovery Studio after molecular dynamics simulation (2D structures).
FIGURE 13
FIGURE 13
Principal component analysis. Projection of the motion for compounds (black) free-SENP1, (red) ZINC79204151, (green) ZINC33916875, and (blue) ZINC85902334.
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