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Network Pharmacology Integrated Molecular Docking and Dynamics to Elucidate Saffron Compounds Targeting Human COX-2 Protein.
Ali, Aarif; Wani, Amir Bashir; Malla, Bashir Ahmad; Poyya, Jagadeesha; Dar, Nawab John; Ali, Fasil; Ahmad, Sheikh Bilal; Rehman, Muneeb U; Nadeem, Ahmed.
Affiliation
  • Ali A; Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST-K, Shuhama, Alusteng, Srinagar 190006, India.
  • Wani AB; Genome Engineering and Societal Biotechnology Lab., Division of Plant Biotechnology, SKUAST-K, Shalimar, Srinagar 190006, India.
  • Malla BA; Department of Biochemistry, School of Biological Sciences, University of Kashmir, Hazratbal, Srinagar 190006, India.
  • Poyya J; SDM Research Institute for Biomedical Sciences, Dharwad 580009, India.
  • Dar NJ; SALK Institute for Biological Studies, La Jolla, San Diego, CA 92037, USA.
  • Ali F; Department of Studies and Research in Biochemistry, Mangalore University, Mangalore 571232, India.
  • Ahmad SB; Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST-K, Shuhama, Alusteng, Srinagar 190006, India.
  • Rehman MU; Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
  • Nadeem A; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Medicina (Kaunas) ; 59(12)2023 Nov 22.
Article in En | MEDLINE | ID: mdl-38138161
ABSTRACT
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.
Subject(s)
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Crocus Limits: Humans Language: En Journal: Medicina (Kaunas) Journal subject: MEDICINA Year: 2023 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Crocus Limits: Humans Language: En Journal: Medicina (Kaunas) Journal subject: MEDICINA Year: 2023 Document type: Article Affiliation country: Country of publication: