High-throughput and computational techniques for aptamer design

INTRODUCTION: Aptamers refer to short ssDNA/RNA sequences that target small molecules, proteins, or cells. Aptamers have significantly advanced diagnostic applications, including biosensors for detecting specific biomarkers, state-of-the-art imaging, and point-of-care technology. Molecular computation helps identify aptamers with high-binding affinity, enabling high-throughput screening, predicting 3D structures, optimizing aptamers for improved stability, specificity, and complex target interactions. AREA COVERED: Aptamers are versatile in the development of specific and sensitive diagnostics. However, there needs to be more understanding of the precise workflow that integrates sequence, structure, and interaction with the target. In this review, the author discusses how significant progress has been made in aptamer discovery using bioinformatics for sequence analysis, docking to model interactions, and MD simulations to account for dynamicity and predict free-energy. Furthermore, the author discusses how quantum chemical calculations are critical for modelling electronic structures and assignin spectroscopic signals. EXPERT OPINION: Incorporating machine learning into the aptamer discovery brings a transformative advancement. With NGS datasets, SELEX, and experimental structures, the implementation of newer workflows yields aptamers with improved binding affinity. Leveraging transfer learning to models using experimental structures and aptamer sequences expands the aptamer design space significantly. As ML continues to evolve, it is poised to become central in accelerating aptamer discovery for biomedical applications in the next 5 years.