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

Abstract 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.