Energy-based method for designing aptamers to target phosphatidylserine

Among existing aptamer design methods, none can address aptamer-target binding energetics during the design phases. A novel aptamer design platform has been proposed to overcome this issue by combining theoretical and computational methods. This is primarily an energy-based platform, focusing on calculating drug-target binding energies (DTBEs) and monitoring the phenomenological energetics of drug-target binding. This relates to understanding the statistical significance of drug-target association/dissociation processes, considering a screened Coulomb interaction (SCI) formalism applied among a distribution of functional charges in a drug-target complex. The interactions of a whole aptamer or any aptamer building block (ABB) (adenine, guanine, cytosine, thymine, or uracil) with the optimal target molecule are considered to calculate DTBEs. Due to various important diagnostic and therapeutic roles in diseases, we chose phosphatidylserine (PS) as our biological target and designed a set of aptamers for it. Using the same technique, concomitantly, we succeeded in discovering aptamers for both lipid and protein biomolecules of therapeutic interest. An aptamer is constructed using a seed-and-grow approach, optimizing SCIs, and selecting the aptamer length based on the trend of DTBE reaching towards equilibrium in a biological environment. This novel aptamer design platform, the 'screened Coulomb interaction approach (SCIA)', ensures the discovery of target-specific aptamers because target specificity is inherently incorporated into the aptamer design phases. Hence, SCIA will significantly enhance aptamer discovery research relevant to dealing with aptamer-based drug discovery for both therapeutic and diagnostic purposes, such as cases where PS is a target biomolecule. Here, our breakthrough achievements are as follows:•An aptamer designing method involving SCIs among charges in a drug-target biomolecule complex to help select ABBs•Nucleic acid aptamers for binding specifically to PS•Aptamer-based therapeutic and diagnostic templates for diseases where PS is a target biomolecule.