Computational modeling of cyanobacterial phytoconstituents against toll-like receptors of skin cancer.
Elhan KhanMahvish KhanSaif KhanMohtashim LohaniNashwa Zaki Ali BusharaHussein Abdul Aziz MaroufKurian PunnooseIffat Zareen AhmadPublished in: Journal of biomolecular structure & dynamics (2023)
Melanoma is an extremely dangerous disease. The diagnosis and treatment of it may be difficult because of its diversity and complexity. More than 90% of the marine biomass (microflora and microalgae) constitutes the natural biodiversity reserves. TLR-related research developments indicate possible cancer therapeutic possibilities. In addition to its significant function in innate immunity, TLR activation is connected to the start of pyroptosis, apoptosis, or autophagy in malignance cells. For these reasons, TLR agonists are appealing candidates for the production of cancer medications. From the web databases, the ternary structures of the receptors (TLR3 and TLR4) and ligands are extracted. Sixty-nine compounds were subjected to a drug likeness filter, but only twenty-two were screened further for evaluating ADMET criteria, in which only seven compounds satisfied the pharmacological properties. These compounds are further analyzed for docking parameters against TLRs (TLR3 and TLR4) and molecular simulation investigation of the best cluster to evaluate the complex stability. Molecular docking methodology discovered that Scytonmein has a significant binding potential energy of -5.21 and -7.92 kcal/mol against TLR3 and TLR4, respectively, in comparison to the redock co-crystal structure (-3.98 and -4.30 kcal/mol, respectively). The simulation analysis demonstrates the significant stability of the Scytonemin and TLR4 complexes in terms of average RMSD and RMSF compared to the redock complex, while criteria like solvent-accessible surface area (SASA), gyration (Rg) and hydrogen bonding have further supported the significant interaction and stability of the conformations.Communicated by Ramaswamy H. Sarma.
Keyphrases
- toll like receptor
- inflammatory response
- immune response
- molecular docking
- nuclear factor
- endoplasmic reticulum stress
- crystal structure
- cell death
- squamous cell carcinoma
- induced apoptosis
- skin cancer
- high resolution
- squamous cell
- gold nanoparticles
- cell proliferation
- binding protein
- drug induced
- data analysis
- virtual reality