In silico Study of shape complementarity, binding affinity, and protein–ligand interactions of systematic evolution of ligands by exponential enrichment-aptamer to programmed death ligand-1 using patchdock

Abstract

BACKGROUND: Nucleic acid aptamers hold great promise in diagnostic and therapeutic applications for a wide range of diseases due to their analog feature to antibodies. Despite the utility of systematic evolution of ligands by exponential enrichment (SELEX) method for aptamer determination, complementarity in silico aptamer design is highly sought after to facilitate virtual screening and increased understanding of important aptamer–protein interactions. MATERIALS AND METHODS: We previously obtained aptamers against programmed death ligand-1 (PD-L1) through SELEX: P12, P32, and P33. In the present work, structure prediction and binding mode of these aptamers to PD-L1 were evaluated using mFold and DNA sequence to structure (IIT Delhi) for two-dimensional and three-dimensional structure prediction, respectively, and PatchDock for docking. PD-L1 model protein 5N2F was used as the target protein. Docking was performed and analyzed based on three aspects: shape complementarity score, binding affinity, and interactions with aptamer. RESULTS: All three aptamers combine steadily with 5N2F protein through strong hydrogen (polar bonds), hydrophobic interactions (nonpolar bonds), and π-cation interactions, which can be accessed through a fully automated protein–ligand interaction profiler. CONCLUSIONS: Molecular docking experiments indicated the feasibility of using in silico technique to select aptamers that can function as antibodies analog.