Investigating DNA Aptamer Binding to Domains of the SARS-CoV-2 Spike Protein: Insights from Molecular Dynamics and MM/PBSA Analysis

In late 2019, a new strain of coronavirus causing severe acute respiratory syndrome (SARS), called SARS-CoV-2, was detected in Wuhan, China. SARS-CoV-2 is primarily transmitted through respiratory droplets via close person-to-person contact. High rates of infection necessitated new approaches to detection, such as via aptamer-based biosensing platforms. Typically, aptamers are generated from a library of single-stranded DNA or RNA fragments through a process called systematic evolution of ligands by exponential enrichment (SELEX). While SELEX is a well-established in vitro technique, there are limited aptamer libraries and the potential for low efficiencies, making the process both time-consuming and costly. Computational approaches alleviate many of these limitations with the proper models and computing power. This study examines the specificity and binding of three aptamers to the S Protein of SARS-CoV-2. Molecular dynamics (MD) simulations assessed solvent-accessible surface areas, radius of gyration, root mean square deviation, and hydrogen bonds. Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) analysis was used to define binding modes, interacting nucleic bases, and energy contributions. Results showed consistent aptamer-protein binding.MM-PBSA results detail the amino acids and nucleic acids bonds throughout the simulation. We conclude that DNA aptamers can recognize and bind to the S protein of SARS-CoV-2, potentially aiding in the development of aptasensors for COVID-19 detection.