44 2033180199

Small molecule PD1 and PDL1 inhibitors

Hai-Feng Ji, Rumman Zaman, Jonathan Xu, Jerica Wilson

A very limited number of small molecule inhibitors targeting PD1/PDL1 signaling pathway have entered clinical trials at this point. We investigated several ligand databases against PD1 and PDL1 separately to evaluate their prospects as potential small molecule PD1/PDL1 inhibitors. Computational studies showed promising results for our hit compounds and some of which are commercially available as well. Three potential small molecule inhibitors for each of PD1 and PDL1 enzyme have been identified based on our structure based virtual screening of ZINC15 ligand database. Proteinligand interactions between our hit compounds and their corresponding target receptors have been analyzed using relevant software which indicates significant binding affinity due formation of hydrogen bond and van der Waals interactions. Predicted ADME properties of all hit compounds have also been determined using online tools. In addition, molecular dynamics simulation has also been performed at one nanosecond to investigate the conformational stability of the protein-ligand complex using GROMACS software. The Root Mean Square Deviation (RMSD) for protein and ligand and Root Mean Square Fluctuation (RMSF) of the protein residues at C-alpha position indicate fair stability

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