The Structure-Based Virtual Screening for Natural Compounds that Bind with the Activating Receptors of Natural Killer Cells

Abstract

AbstractAimThis study is aimed at prospecting for natural compounds that have strong binding affinity for the Activating Receptors of Natural Killer (NK) cells.BackgroundNK cells are responsible for the immunosurveillance of tumor and virally- infected cells. The cytotoxic potentials of this unique population of immune cells are triggered by the activating receptors. Through ligand-binding, these receptors induce the tyrosine phosphorylation of adapter proteins through their Immunoreceptor Tyrosine–based Activation Motif ITAM sequences and this triggers direct cytotoxicity and the production of cytokines through different signal pathways.ObjectiveTo computationally predict the selectivity, specificity, and efficacy of natural compounds to be used as immunostimulatory agents for cancer treatment.MethodIn this study, 1,697 natural compounds were obtained from 82 edible tropical plants through data mining. The molecular docking simulations of these compounds were executed against 18 activating NK cells receptor targets using the Python Prescription 0.8. An arbitrary docking score ≥ −7.0 kcal/mol was chosen as cut off value. Further screening for oral bioavailability, promiscuity, molecular complexity and pharmacokinetic properties using the Swissadme and pkCSM webservers. The ligand similarity analysis and phylogenetic analysis of the receptors was carried out with the ChemMine and Clustal Omega webservers respectively. Binding site analyses and bioactivity prediction were also done with the Protein-Ligand Interaction Profiler and Molinspiration webservers respectively. Normal mode analyses were carried out with the CABS-flex 2.0 server.ResultSeventeen bioactive and non-promiscuous lead compounds with good physicochemical and pharmacokinetic properties were identified.ConclusionFurther tests are required to evaluate the efficacy of the lead compounds.