IN SILICO SCREENING AND MOLECULAR DYNAMIC SIMULATION STUDIES OF POTENTIAL SMALL MOLECULE IMMUNOMODULATORS OF THE KIR2DS2 RECEPTOR

Abstract

AbstractThe World Health Organization reports that cancer is one of the most common causes of death worldwide and it accounted for an estimated 9.6 million deaths in 2018. As compared with chemotherapy or radiotherapy, immunotherapy offers a safer, less stressful and selective strategy in the destruction of cancer cells. The killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) expressed on Natural Killer (NK) cells are involved in signal transduction processes that produce pro-inflammatory cytokines and directly destroy cancer and virally infected cells. The aim of this study is to identify small molecules from natural products that have strong binding affinity with KIR2DS2 and possible bioactivity. A library of small molecule natural compounds obtained from edible African plants was used for in Silico molecular docking simulations of KIR2DS2 (PDBID: 1m4k) using Pyrx. An arbitrary docking score ≥ −7.0 kcal/mol was chosen as cut off value. Screening for drug-likeness and ligand efficiency was based on the molecular descriptors of the compounds as provided by Pubchem. Further screening for saturation, molar refractivity, promiscuity, pharmacokinetic properties, and bioactivity was done using SWISSADME, PKCSM, and Molinspiration respectively. The molecular dynamic simulation and analyses was done using the Galaxy webserver which uses the GROMACS software. Analyses of molecular dynamic simulation were done using Galaxy and MDWEB webservers. Gibberellin A20 and A29 were obtained as the lead compounds and they show better promise as drug candidates for KIR2DS2 than the standard. It is recommended that the immuno-stimulatory effect of the lead compounds on KIR2DS2 be further investigated.