Potential of paracetamol for reproductive disruption: molecular interaction, dynamics, and MM-PBSA based <i>in-silico</i> assessment

Abdi, Sayed Aliul Hasan; Ali, Abuzer; Sayed, Shabihul Fatma; Ali, Amena; Abadi, Shaivad Shabee Hulhasan; Tahir, Abu; Afzal, Mohammad Amir; Rashid, Hina; Aly, Omar M.; Nagarajan, Sumathi

doi:10.1080/15376516.2022.2137872

Cited by 1 publication

(5 citation statements)

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“…Analyses of simulation convergence were conducted in terms of the root mean square deviation (RMSD), the radius of gyration (RG), the root mean square fluctuation (RMSF), and the solvent-accessible surface area (SASA), which were calculated using g_rmsf, g_gyrate, and g_hbond plugins of GROMACS, respectively [ 5 , 10 , 11 , 12 , 13 ]. In addition, PCA was also calculated from the trajectories.…”

Section: Resultsmentioning

confidence: 99%

“…The quantitative evaluation of the substrate molecule interaction mechanism for the entire assessment is provided by MM-PBSA. The binding free energy (ΔG), van der Waals energy, and electrostatic energy with hexaconazole in comparison with dihydrotestosterone and aminoglutethimide were calculated [ 10 ]. The details are given in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

“…; It has been also endorsed by experimental studies that hexaconazole has the potency to disrupt normal endocrine or reproductive hormone homeostasis by causing abnormal hormonal synthesis. Furthermore, SASA and PCA reflect the surface area of a protein that interacts with its solvent molecules and the total expansion of a protein during MD simulation, respectively [ 10 ]. Our results reveal that SHBG and the hexaconazole complex have SASA values almost similar to SHBG native ligand dihydrotestosterone and inhibitor aminoglutethimide.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, 30 ns of MD was run to examine the stability of each system. MD was performed 3 times to verify the MD findings [ 10 , 11 , 12 , 13 ]. The details related to the set-up of MD simulations are given in Table 4 .…”

Section: Methodsmentioning

confidence: 99%

“…ΔG represents the binding free energy of the ligand (hexaconazole, dihydrotestosterone, and aminoglutethimide) with SHBG, G protein represents the SHBG binding energy, and G represents the ligand [ 10 ].…”

Section: Methodsmentioning

confidence: 99%

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Potency of Hexaconazole to Disrupt Endocrine Function with Sex Hormone-Binding Globulin

Alquraini

2023

IJMS

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Hexaconazole is widely used as a fungicide for agricultural purposes. However, the endocrine-disrupting potential of hexaconazole is still under investigation. In addition, an experimental study found that hexaconazole may disrupt the normal synthesis of steroidal hormones. The potency of hexaconazole to bind with sex hormone-binding globulin (SHBG), a plasma carrier protein that binds androgens and oestrogens, is unknown. In this study, we evaluated the efficacy of hexaconazole to bind with SHBG by molecular interaction, a molecular dynamics method. In addition, principal component analysis was performed to understand the dynamical behaviour of hexaconazole with SHBG in comparison with dihydrotestosterone and aminoglutethimide. The binding scores of hexaconazole, dihydrotestosterone, and aminoglutethimide with SHBG were found to be −7.12 kcal/mol, −11.41 kcal/mol, and −6.84 kcal/mol, respectively. With respect to stable molecular interaction, hexaconazole showed similar molecular dynamics patterns of root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding. The solvent surface area (SASA) and principal component analysis (PCA) of hexaconazole exhibit similar patterns in comparison with dihydrotestosterone and aminoglutethimide. These results show that hexaconazole has a stable molecular interaction with SHBG, which may acquire the active site of the native ligand, resulting in significant endocrine disruption during agricultural work.

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