Application and evaluation of molecular docking for aptamer and small molecular interaction- A case study with tetracycline antibiotics

Molecular docking (MD) analysis is currently the most commonly used theoretical simulation method to investigate the interaction of aptamers (receptors) and small molecules (ligands) and understand the recognition mechanism between them at a molecular level. Using the specific aptamers of tetracycline antibiotics (tetracycline (TET), oxytetracycline (OTC), doxycycline (DOC)) as the docking models, three steady-state aptamers of tertiary structures (SATS) were established for each aptamer with the UNAFold and RNAComposer tools. The binding free energy (BFE), docking score (DS), and binding site (base) of the specific ligands (TET, OTC, and DOC) with their respective SATS were obtained by molecular docking. The results revealed one or more binding sites in the established SATS of the aptamers. The BFE and DS of different binding sites of one specific SATS varied significantly. The results also revealed that the site with the highest BFE represented the most dominant binding site, even if it was not the SATS with minimum energy. The BFE values could also be used to evaluate the affinity and specificity of the aptamer to its target. For the first time, this study proposes a method for MD analysis of the aptamer and its target based on different SATS, clarification of the binding mode, and prediction of the binding sites (bases). This study provides a theoretical basis for tailoring; structural optimization; and base modification of aptamers; identifying aptamers with high affinity and specificity.

Automated summary

Molecular docking (MD) analysis is widely used for studying the interaction between aptamers and small molecules. This study established steady-state aptamers of tertiary structures (SATS) using specific aptamers of tetracycline antibiotics as docking models. Molecular docking results revealed multiple binding sites in the SATS of aptamers, with significant variations in binding free energy (BFE) and docking score (DS). The study also proposed a method for MD analysis based on SATS, providing insights into binding mode and predicting binding sites.