Biochemical and Computational Assessment of Acute Phase Proteins in Dairy Cows Affected with Subclinical Mastitis

Ali, Aarif; Rehman, Muneeb U.; Mushtaq, Saima; Ahmad, Bilal; Khan, Altaf; Karan, Anik; Wani, Amir Bashir; Ganie, Showkat Ahmad; Mir, Manzoor Ur Rahman

doi:10.3390/cimb45070338

Cited by 5 publications

(1 citation statement)

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“…In this study, ADMET properties were used to determine the pharmacokinetics of drugs in the body. The five parameters of Lipinski's rule were used to determine the drug-like properties of compounds, and these features are mostly important as they are related to dissolution and intestinal permeability [39,[53][54][55]. In our study, all the molecules followed Lipinski's rule except rutin, which has a molecular weight >500 g/mol, a number of hydrogen bond donors >5, and a number of acceptors >10.…”

Section: Discussionmentioning

confidence: 91%

Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein

Ali,

Wani,

Malla

et al. 2023

Medicina

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Background and Objectives: Cyclooxygenase-2 (COX-2) is mostly linked to inflammation and has been validated as a molecular target for treating inflammatory diseases. The present study aimed to identify novel compounds that could inhibit COX-2, which is associated with various diseases including inflammation, and in such a scenario, plant-derived biomolecules have been considered as attractive candidates. Materials and Methods: In the present study, physiochemical properties and toxicity of natural compounds/drugs were determined by SWISSADME and ProTox-II. In the present study, the molecular docking binding features of saffron derivatives (crocetin, picrocrocin, quercetin, safranal, crocin, rutin, and dimethylcrocetin) against human COX-2 protein were assessed. Moreover, protein-protein interactions, topographic properties, gene enrichment analysis and molecular dynamics simulation were also determined. Results: The present study revealed that picrocrocin showed the highest binding affinity of −8.1 kcal/mol when docked against the COX-2 protein. PROCHECK analysis revealed that 90.3% of the protein residues were found in the most favored region. Compartmentalized Protein–Protein Interaction identified 90 interactions with an average interaction score of 0.62, and the highest localization score of 0.99 found in secretory pathways. The Computed Atlas of Surface Topography of Proteins was used to identify binding pockets and important residues that could serve as drug targets. Use of WEBnmα revealed protein dynamics by using normal mode analysis. Ligand and Receptor Dynamics used the Molecular Generalized Born Surface Area approach to determine the binding free energy of the protein. Gene enrichment analysis revealed that ovarian steroidogenesis, was the most significant enrichment pathway. Molecular dynamic simulations were executed for the best docked (COX-2-picrocrocin) complex, and the results displayed conformational alterations with more pronounced surface residue fluctuations in COX-2 with loss of the intra-protein hydrogen bonding network. The direct interaction of picrocrocin with various crucial amino-acid residues like GLN203, TYR385, HIS386 and 388, ASN382, and TRP387 causes modifications in these residues, which ultimately attenuates the activity of COX-2 protein. Conclusions: The present study revealed that picrocrocin was the most effective biomolecule and could be repurposed via computational approaches. However, various in vivo and in vitro observations are still needed.

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Section: Discussionmentioning

confidence: 91%