Molecular Docking and 3D-QSAR Studies on a Series of Benzenesulfonamide Derivatives as a Hepatitis B Virus Capsid Assembly Inhibitor

Ma, Chao; Liu, Wenguang; Liu, Wen-ding; Xi, Chang-cheng; Xiong, Fei; Zhang, Shuping

doi:10.1080/10406638.2020.1871038

Cited by 13 publications

(5 citation statements)

References 31 publications

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“…To construct the pharmacophore model, a series of isoxazole compounds acting as FXR agonists were chosen from previously published studies (US11718619, US10793568). The experimental data obtained were all measured under the same experimental conditions, and the experimental data (EC 50 ) were measured using the fluorescent resonance energy transfer (FRET) method [ 44 ]. The FRET signal is measured as the ratio of 520 nm/495 nm emission following excitation at 340 nm.…”

Section: Methodsmentioning

confidence: 99%

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists

Yan,

Yang,

Shen

et al. 2024

Molecules

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The farnesoid X receptor (FXR) has been recognized as a potential drug target for the treatment of non-alcoholic fatty liver disease (NAFLD). FXR agonists benefit NAFLD by modulating bile acid synthesis and transport, lipid metabolism, inflammation, and fibrosis pathways. However, there are still great challenges involved in developing safe and effective FXR agonists. To investigate the critical factors contributing to their activity on the FXR, 3D-QSAR molecular modeling was applied to a series of isoxazole derivatives, using comparative molecular field analysis (CoMFA (q2 = 0.664, r2 = 0.960, r2pred = 0.872)) and comparative molecular similarity indices analysis (CoMSIA (q2 = 0.706, r2 = 0.969, r2pred = 0.866)) models, which demonstrated strong predictive ability in our study. The contour maps generated from molecular modeling showed that the presence of hydrophobicity at the R2 group and electronegativity group at the R3 group in these compounds is crucial to their agonistic activity. A molecular dynamics (MD) simulation was carried out to further understand the binding modes and interactions between the FXR and its agonists in preclinical or clinical studies. The conformational motions of loops L: H1/H2 and L: H5/H6 in FXR–ligand binding domain (LBD) were crucial to the protein stability and agonistic activity of ligands. Hydrophobic interactions were formed between residues (such as LEU287, MET290, ALA291, HIS294, and VAL297) in helix H3 and ligands. In particular, our study found that residue ARG331 participated in salt bridges, and HIS447 participated in salt bridges and hydrogen bonds with ligands; these interactions were significant to protein–ligand binding. Eight new potent FXR agonists were designed according to our results, and their activities were predicted to be better than that of the first synthetic FXR agonist, GW4064.

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Section: Methodsmentioning

confidence: 99%

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists

Yan,

Yang,

Shen

et al. 2024

Molecules

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“…The energy minimization of fifty compounds was optimized using Gasteiger–Hückel charges and the standard Tripos force field with an energy gradient convergence criterion of 0.005 kcal (mol Å) −1 . 18 Furthermore, energy minimizations were performed using the Powell method 1000 maximum iterations. 19,20 Other parameters use the default values.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of novel HIV-1 protease inhibitors with DRV-resistance by utilizing 3D-QSAR molecular docking and molecular dynamics simulation

Zhang

Chen

et al. 2022

New J. Chem.

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“…rcsb.org). [30] Then, the protein was prepared using the protein preparation module in SYBYLÀ X 2.0, which involved adding hydrogens, a process was executed in which all amino acid residues found at the side chain and main chain's end were repaired before finally adding the charge. Following this, an energy minimization process was done on the structure.…”

Section: Molecular Dockingmentioning

confidence: 99%

Design of New Second‐Generation TRK Inhibitors Targeting Tropomyosin Receptor Kinases by Using Molecular Docking, Molecular Dynamics Simulations and ADMET Properties

Zhao,

Cui,

Tang

et al. 2024

ChemistrySelect

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TRK, as a type of cell surface protein, plays a critical role in various biological processes, particularly as a key target for cancer treatment. We explored the correlation between the structure and activity of indole‐2‐one derivatives through investigations involving 3D‐QSAR molecular modelling, molecular docking, molecular dynamics, and ADMET property research. The statistical data from the CoMFA and CoMSIA models exhibit excellent internal stability (CoMFA: q2=0.622, r2=0.992; CoMSIA: q2=0.740, r2=0.972). Further molecular docking unveiled the interaction mechanism between small molecules and receptor proteins, demonstrating that the hydrogen bonding between amino acids Met590 and Glu592 and small molecules could enhance the ligand‐receptor binding affinity. Based on the 3D‐QSAR model and molecular docking, we designed and predicted the activity of eight new molecules, which displayed high expected activity. Subsequently, through 100 ns MD simulations and binding free energy calculations, we affirmed the stability of the molecular docking results. Finally, we employed ADMET to predict the pharmacokinetic properties of the newly designed molecules, validating their commendable drug‐like characteristics. These research findings provide valuable references for the design and development of novel TRK inhibitors, offering fresh perspectives for subsequent drug design.

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Molecular Docking and 3D-QSAR Studies on a Series of Benzenesulfonamide Derivatives as a Hepatitis B Virus Capsid Assembly Inhibitor

Cited by 13 publications

References 31 publications

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists

3D-QSAR and Molecular Dynamics Study of Isoxazole Derivatives to Identify the Structural Requirements for Farnesoid X Receptor (FXR) Agonists

Evaluation of novel HIV-1 protease inhibitors with DRV-resistance by utilizing 3D-QSAR molecular docking and molecular dynamics simulation

Design of New Second‐Generation TRK Inhibitors Targeting Tropomyosin Receptor Kinases by Using Molecular Docking, Molecular Dynamics Simulations and ADMET Properties

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