Energy-based method for designing aptamers to target phosphatidylcholine

• Aptamer designing method involving screened Coulomb interactions among charges in a drug-target biomolecule complex. • Designing nucleic acid aptamers for binding specifically to phosphatidylcholine. • Creating an aptamer-based therapeutic template for various diseases. Diverse technologies are used to design nucleic acid aptamers to achieve targeted therapeutics, engineer diagnostic tools to detect specific biomolecules associated with disease-oriented signaling pathways, and develop drug delivery systems. Despite the availability of many methods, including systematic evolution of ligands by exponential enrichment, there is no reliable method that can address aptamer-target binding energetics during aptamer design. We have developed a technique to do so, combining theoretical and computational methods. In this energy-based method, we calculate drug-target binding energies (DTBEs) and monitor phenomenological drug-target binding energetics related to drug-target association/dissociation processes, considering screened Coulomb interactions (SCIs) among a distribution of functional charges in a complex of an aptamer or aptamer building block (ABB) and target biomolecule in the biological environment where interactions take place. An ABB is any nucleotide: adenine, guanine, cytosine, uracil (for RNA), or thymine (for DNA). We have designed a set of novel aptamers for phosphatidylcholine, an important biomolecule relevant to various therapeutics, that are outlined here. In summary, our drug designing method involves constructing an aptamer using a seed-and-grow approach, optimizing SCIs, and selecting aptamer length based on the trend of DTBE in an aqueous environment, where aptamers interact with target(s). This novel technique, the screened Coulomb interaction approach (SCIA), ensures the discovery of target-specific aptamers as the target specificity is inherently incorporated during the aptamer design phases. SCIA is expected to significantly enhance aptamer discovery research and help develop aptamer-based therapeutics for diseases where specific drug targets are known.