Structural Insights of PD-1/PD-L1 Axis: An Approach.

Background: Interaction of PD-1 protein (present on immune T-cell) with its ligand PD-L1 (over-expressed on cancerous cell) makes the cancerous cell survive and thrive. The association of PD-1/PD-L1 represents a classical protein-protein interaction (PPI), where receptor and ligand binding through a large flat surface. Blocking the PD-1/PDL-1 complex formation can restore the normal immune mechanism, thereby destroying cancerous cells.

Computational Exploration of Naturally Occurring Flavonoids as TGF-β Inhibitors in Breast Cancer: Insights from Docking and Molecular Dynamics Simulations and In-vitro Cytotoxicity Study.

Breast cancer is a global health concern, demanding innovative treatments. Targeting the Transforming Growth Factor-beta (TGF-β) signaling pathway, pivotal in breast cancer, is a promising approach. TGF-β inhibits proliferation via G1 phase cell cycle arrest, acting as a suppressor initially, but in later stages, it promotes progression by enhancing motility, invasiveness, and metastasis formation.

New molecular insights for 4-1,2,4-triazole derivatives as inhibitors of tankyrase and Wnt-signaling antagonist: a molecular dynamics simulation study.

Tankyrase (TNKS) enzymes remained central biotargets to treat Wnt-driven colorectal cancers. The success of Olaparib posited the druggability of PARP family enzymes depending on their role in tumor proliferation. In this work, an MD-simulation-based comparative assessment of the protein-ligand interactions using the best-docked poses of three selected compounds (two of the designed and previously synthesized molecules obtained through molecular docking and one reported TNKS inhibitor) was performed for a 500 ns period.

Identification of 1,2,4-Oxadiazoles-Based Novel EGFR Inhibitors: Molecular Dynamics Simulation-Guided Identification and in vitro ADME Studies.

Background: In this work, we have identified heterocyclic derivatives with 1,2,4 oxadiazole scaffold mimicking the functions of tyrosine kinase inhibitors. Fourteen molecules that displayed the best fit were picked from the library of compounds and studied under in-silico and in-vitro conditions. Four compounds were selected for further cytotoxicity and ADME (Absorption, Distribution, Metabolism, Elimination) profiling showing IC (from 8-13 µM) values against EGFR positive cancer cell line (MCF7).

Rational design-aided discovery of novel 1,2,4-oxadiazole derivatives as potential EGFR inhibitors.

A molecular dynamics-based sampling of epidermal growth factor receptor tyrosine kinase (EGFR-TK) was carried out to search for energetically more stable protein, which was then used for molecular docking of a series of 1,2,4-oxadiazole derivatives previously reported from our laboratory. A total of 14 compounds were docked, where compounds 6a and 6b showed better binding to EGFR in silico. Further, physicochemical properties of all the compounds were calculated, which suggested that all the molecules obeyed Lipinski's rule of 5 and had favorable polar surface area and CaCO2 permeability along with the low potential for HERG inhibition.

Protein kinase C βII in diabetic complications: survey of structural, biological and computational studies.

Introduction: PKC-βII is a conventional isoform of PKC. It is overexpressed in hyperglycemic conditions and is known to trigger various diabetic complications, mainly cardiovascular complications and to a certain extent nephropathy, neuropathy, retinopathy etc. Selective inhibition of this enzyme will be one of the favorable approaches to treat diabetes-mellitus-related complications.