Lysozyme and Human Serum Albumin Proteins as Potential Nitric Oxide Cardiovascular Drug Carriers: Theoretical and Experimental Investigation

Nassab, Chahlaa; Arooj, Mahreen; Shehadi, Ihsan A.; Parambath, Javad B. M.; Kanan, Sofian M.; Mohamed, Ahmed A.

doi:10.1021/acs.jpcb.1c04614

Cited by 13 publications

(10 citation statements)

References 60 publications

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“…Molecular dynamics (MD) simulations are extensively used to explore the stability and binding of various protein ligand complexes [28][29][30]. In order to elucidate the stability of complex structures, both proteins were bound with best binding compound 3 and subjected to MD simulations.…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

et al. 2022

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A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS ) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (–8.4 and –9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.

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Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

et al. 2022

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“…Visual inspection of the apo and holo crystal structures of the protein crowders shows that myoglobin does not have a crevice or buried binding site for small molecules larger than molecular oxygen, whereas HEWL and BSA do. Moreover, HEWL and BSA were shown to bind to small molecules and act as potential drug carriers (41,46,47).…”

Section: Gsk3 Inhibitor Sb216763mentioning

confidence: 99%

Diffusion of small molecule drugs is affected by surface interactions and crowder proteins

Dey

Nunes-Alves

Wade

et al. 2021

Preprint

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Crowded environments affect the pharmacokinetics of drug molecules. Here, we investigate how three macromolecular protein crowders, bovine serum albumin, hen egg-white lysozyme and myoglobin, influence the translational diffusion rates and interactions of four low molecular-weight drugs, fluorescein, doxorubicin, glycogen synthase kinase-3 inhibitor SB216763 and quinacrine. Using Fluorescence Recovery After Photo-bleaching in Line mode (Line FRAP), Brownian dynamics simulations and molecular docking, we find that the diffusive behavior of the small molecules is highly affected by self-aggregation, interactions with the proteins, and surface adhesion. Fluorescein diffusion is decreased by protein crowders due to their interactions. On the other hand, for doxorubicin, the presence of protein crowders increases diffusion by reducing surface interactions. SB216763 shows a third scenario, where BSA, but not myoglobin or lysozyme, reduces self-aggregation, resulting in faster diffusion. Quinacrine was the only small molecule whose diffusion was not affected by the presence of protein crowders. The mechanistic insights gained here into the effects of interactions of small molecules with proteins and surfaces on the translational diffusion of small molecules can assist in optimizing the design of compounds for higher mobility and lower occlusion in complex macromolecular environments.

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“…This type of study also helps to understand how drugs interact with serum proteins or other binding targets in the blood plasma. [20,21] Hemoglobin (Hb) is another important protein present in blood cells. It is the most abundant component of the red blood cells accounting for around 92 % consisting of four subunits with one heme category with a polypeptide chain on every subunit.…”

Section: Introductionmentioning

confidence: 99%

“…The interaction of drug‐serum albumin is an extensively researched area to derive various informations on the pharmacokinetics and pharmacodynamics of the drug molecules and provide a base to further exploit the far‐reaching pharmaceutical potential of their potential derivatives. This type of study also helps to understand how drugs interact with serum proteins or other binding targets in the blood plasma [20,21] …”

Section: Introductionmentioning

confidence: 99%

Elucidating the Interaction and Stability of Withanone and Withaferin‐A with Human Serum Albumin, Lysozyme and Hemoglobin Using Computational Biophysical Modeling

2022

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Withania somnifera consists of various bioactive compounds, of which withanone (WT−N) and withaferin‐A (WT−A) are known to have many therapeutic properties. To understand drug metabolism and transportation methods, binding of endogenous and exogenous ingredients with transport proteins is of utmost importance. Therefore, to perceive the molecular recognition mechanism of WT−N and WT−A, the association of human serum albumin, human hemoglobin and human lysozyme with WT−N and WT−A were examined, using various in silico techniques. For our study, we have employed both quantum mechanics and molecular mechanics approaches. Resultantly, drug‐like properties and reactivity were calculated with WT−N and WT−A being the most reactive among all the withanolides. The protein HSA in presence of WT−N showed more stability than that of WT−A. However, HL and Hb showed better stability with WT−A as compared to WT−N. Several non‐covalent interactions contributed the utmost part in the binding of WT−N and WT−A with the proteins. The MD simulation studies also showed evidence in the conformational changes and other dynamical properties of the three proteins with both the ligands. Finally, MM‐PBSA results confirmed the free binding energy of the complexes. Our study has provided a substantial recognition of bioactive molecules WT−N and WT−A binding with the carrier proteins, which can significantly affect the pharmacokinetics of these molecules.

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Lysozyme and Human Serum Albumin Proteins as Potential Nitric Oxide Cardiovascular Drug Carriers: Theoretical and Experimental Investigation

Cited by 13 publications

References 60 publications

Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

Diffusion of small molecule drugs is affected by surface interactions and crowder proteins

Elucidating the Interaction and Stability of Withanone and Withaferin‐A with Human Serum Albumin, Lysozyme and Hemoglobin Using Computational Biophysical Modeling

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