The potential of phytochemicals against epidermal growth factor receptor tyrosine kinase (EGFRK): an insight from molecular dynamic simulations.

Cancer is an umbrella term used to define various diseases with abnormal cell proliferation at the focal point. According to the WHO, cancer is the leading cause of death worldwide, with lung cancer being the second most common perpetrator after breast cancer. There are several proteins acting in harmony that lead to cancer. EGFR has been identified as one of the proteins that is linked to cell division, even when it is cancerous in nature. Cancer can be treated using therapeutic agents that target EGFR or their signaling networks. Available drugs that could inhibit EGFR have acquired resistance in most cases and multiple side effects on the human body. That is why phytochemicals are being studied for their role in this case. Around 8000 compounds were retrieved from our previously created phytochemdb database for their drug activity, and the 3D protein structure was collected from the protein data bank. The selected dataset of ligands was virtually screened through HTVS, SP, and XP to retain the top 4 hits. Molecular dynamics revealed the stability and flexibility of protein-(selected)ligand interactions. The non-bond interactions of each of the compounds with EGFR, such as Gossypetin interacting with active site MET769 and ASP831; Muxiangrine III interacting with MET769 and ASP831; Quercetagetin showing non-bonded interactions with GLU738, GLN767, and MET769 for >100% of the simulation timeframe These findings suggest further research into these compounds, which can yield a potential phytochemical drug against cancer.Communicated by Ramaswamy H. Sarma.

Molecular dynamics-based insight of VEGFR-2 kinase domain: a combined study of pharmacophore modeling and molecular docking and dynamics.

BACKGROUND: Inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase by small molecules has become a promising target in the treatment of cancer. OBJECTIVE: In this study, we approached pharmacophore modeling coupled with a structure-based virtual screening workflow to identify the potent inhibitors. METHODS: The top selected hit compounds have been rescored using the MM/GBSA approach. To understand the molecular reactivity, electronic properties, and stability of those inhibitors, we have employed density functional theory and molecular dynamics. Following that, the best 21 hit compounds have been further post-processed with a Quantum ligand partial charge-based rescoring process and further validated by implementing molecular dynamics simulation. RESULTS: The ten hit compounds have been hypothesized and considered as potent inhibitors of VEGFR-2 tyrosine kinase. This study also signifies the contribution of QM-based ligand partial charge, which is more accurate in predicting reliable free binding energy and filtering large ligand libraries to hit optimization, rather than assigning those of the force field-based method. From the binding pattern analysis of all the complexes, amino acids, such as Glu885, Cys919, Cys1045, Thr916, Thr919, and Asp1046, were found to have comprehensive interaction with the hit compounds. CONCLUSION: Hence, this could prove to be useful as a potential inhibition site of the VEGFR-2 tyrosine kinase domain for future researchers. Moreover, this study also emphasizes the conformational changes upon ATP binding, based on either the receptor's rigidity or flexibility.

Physicochemical characteristics, sensory profile, probiotic, and starter culture viability of synbiotic yogurt.

Objectives: This study aimed to envisage the effectiveness of adding three particular prebiotics (inulin, ß-glucan, and Hi-maize) to synbiotic yogurt's physicochemical properties, sensory characteristics, and survivability of the probiotic and starter cultures. Materials and Methods: The yogurt's gross composition, syneresis, water-holding capacity (WHC), viscosity, sensorial properties, and probiotic and starter cell stability were analyzed. The Lactobacillus delbrueckii subsp. bulgaricus M240-5 and Streptococcus thermophilus M140-2 were employed as yogurt starter bacteria, and Lactobacillus acidophilus LA-5 as probiotic culture. The synbiotic yogurt was formulated with 5% sucrose and 0.7% artificial vanilla flavor. Results: The findings showed that when prebiotic ingredients were added to synbiotic yogurt, it had a significant impact on its sensory qualities, WHC, syneresis, and viscosity when compared to plain yogurt samples. The prebiotics did not affect the pH and titratable acidity of the yogurt samples. Additionally, the prebiotic supplementation did not influence the protein and fat content of synbiotic yogurt (p < 0.05). Prebiotics had an impact on the probiotic cell viability and total viable count (p < 0.05) compared to the plain sample, the 2.5% ß-glucan, 1.5% and 2.5% Hi-maize samples had the highest mean viability (8.95 Log CFU/ml). The starter culture ratio remained stable in response to the prebiotic levels. Conclusion: In summary, the production of synbiotic yogurts supplemented with Hi-maize and ß-glucan at 1.5% and 2.5%, respectively, is highly advised because these supplementations provide yogurt with acceptable syneresis, viscosity, WHC, and sensory attributes.