Structural aspects of formetanate hydrochloride binding with human serum albumin using spectroscopic and molecular modeling techniques

Singh, Shweta; Gopi, Priyanka; Pandya, Prateek

doi:10.1016/j.saa.2022.121618

Cited by 15 publications

(8 citation statements)

References 43 publications

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“…33,34 These MD simulations were performed in triplicate, and the data were analyzed using VMD 1.9.3 and Biovia Discovery Studio software. 21,41,42…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

“…52 Using Gauss View 5.0, TMT from the docked and MD pose was extracted and converted to a legible Gaussian format. 21,53 Structure optimization and single point energies were calculated using the B3LYP/6-311**g(d,p) basis set. The structural differences of TMT conformations from the gas phase, docked pose, and MD pose were compared.…”

Section: Qm Optimization and Energy Calculationsmentioning

confidence: 99%

“…It is responsible for the primary activity of transporting many endogenous and exogenous ligands such as fatty acids, amino acids toxic chemicals, and drugs throughout the body 18,19 . Thus, interacting with the protein, these ligands such as pesticides can alter protein shape and function which causes harmful consequences 20–25 . As ligand distribution, metabolism toxicity, and dosage correlate with binding affinity concerning HSA in the blood, studying their interactions with HSA is of utmost importance 26–28 …”

Section: Introductionmentioning

confidence: 99%

“…18,19 Thus, interacting with the protein, these ligands such as pesticides can alter protein shape and function which causes harmful consequences. [20][21][22][23][24][25] As ligand distribution, metabolism toxicity, and dosage correlate with binding affinity concerning HSA in the blood, studying their interactions with HSA is of utmost importance. [26][27][28] In light of TMT's extremely harmful carcinogenic and neurodegenerative consequences for the human body, understanding the binding interactions of TMT is necessary with HSA as many of these molecules are carried throughout the body via binding with HSA.…”

mentioning

confidence: 99%

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Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Singh,

Gopi,

Rani

et al. 2024

J of Molecular Recognition

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Tetramethrin (TMT) is a commonly used insecticide and has a carcinogenic and neurodegenerative effect on humans. The binding mechanism and toxicological implications of TMT to human serum albumin (HSA) were examined in this study employing a combination of biophysical and computational methods indicating moderate binding affinity and potential hepato and renal toxicity. Fluorescence quenching experiments showed that TMT binds to HSA with a moderate affinity, and the binding process was spontaneous and predominantly enthalpy‐driven. Circular dichroism spectroscopy revealed that TMT binding did not induce any significant conformational changes in HSA, resulting in no changes in its alpha‐helix content. The binding site and modalities of TMT interactions with HSA as computed by molecular docking and molecular dynamics simulations revealed that it binds to Sudlow site II of HSA via hydrophobic interactions through its dimethylcyclopropane carboxylate methyl propanyl group. The structural dynamics of TMT induce proper fit into the binding site creating increased and stabilizing interactions. Additionally, molecular mechanics–Poisson Boltzmann surface area calculations also indicated that non‐polar and van der Waals were found to be the major contributors to the high binding free energy of the complex. Quantum mechanics (QM) revealed the conformational energies of the binding confirmation and the degree of deviation from the global minimum energy conformation of TMT. The results of this study provide a comprehensive understanding of the binding mechanism of TMT with HSA, which is important for evaluating the toxicity of this insecticide in humans.

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“…33,34 These MD simulations were performed in triplicate, and the data were analyzed using VMD 1.9.3 and Biovia Discovery Studio software. 21,41,42…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Section: Qm Optimization and Energy Calculationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Singh,

Gopi,

Rani

et al. 2024

J of Molecular Recognition

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“…The structure and coordinate files for VLB, DD, and HSA were generated using VMD 1.9.3 software 37 and the parameter files were generated using CHARMM GUI. 38,39 We used the standard MD protocol for solvation, equilibration and production run as reported earlier 40,41 wherein the complex was solvated using the TIP3P water model and neutralized by adding NaCl ions. The ionized structure was minimized for 5000 steps and equilibrated by NVT and NPT for 1 ns each.…”

Section: Molecular Dynamics and Conformational Analysismentioning

confidence: 99%

Thermodynamic and structural profiles of multi‐target binding of vinblastine in solution

Gopi

Singh

Islam

et al. 2022

J of Molecular Recognition

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Structural information about drug‐receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi‐target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR‐5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR‐5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H‐bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.

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Identification of multi-targeting natural antiviral peptides to impede SARS-CoV-2 infection

et al. 2022

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SARS-CoV-2 and its variants cause serious health concerns throughout the world. The alarming increase in the daily number of cases has become a nightmare in many low-income countries; although some vaccines are available, their high cost and low vaccine production make them unreachable to ordinary people in developing countries. Other treatment strategies are required for novel therapeutic options. The peptide-based drug is one of the alternatives with low toxicity, more specificity, and ease of synthesis. Herein, we have applied structure-based virtual screening to identify potential peptides targeting the critical proteins of SARS-CoV-2. Non-toxic natural antiviral peptides were selected from the enormous number of peptides. Comparative modeling was applied to prepare a 3D structure of selected peptides. 3D models of the peptides were docked using the ClusPro docking server to determine their binding affinity and peptide-protein interaction. The high-scoring peptides were docked with other crucial proteins to analyze multiple targeting peptides. The two best peptides were subjected to MD simulations to validate the structure stability and evaluated RMSD, RMSF, Rg , SASA, and H-bonding from the trajectory analysis of 100 ns. The proposed lead peptides can be used as a broad-spectrum drug and potentially develop as a therapeutic to combat SARS-CoV-2, positively impacting the current pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s11224-022-02113-9.

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Structural aspects of formetanate hydrochloride binding with human serum albumin using spectroscopic and molecular modeling techniques

Cited by 15 publications

References 43 publications

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Biophysical and structural characterization of tetramethrin serum protein complex and its toxicological implications

Thermodynamic and structural profiles of multi‐target binding of vinblastine in solution

Identification of multi-targeting natural antiviral peptides to impede SARS-CoV-2 infection

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