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Aptamers are oligonucleotide-based bioreceptors that are selected in vitro from randomized libraries to bind specific molecules with high affinity, and are proving popular for applications in diagnostics, bioimaging, and therapeutics. A better understanding of aptamer-ligand interactions could facilitate sequence engineering efforts to improve aptamer binding properties, and perhaps eventually allow for the direct design of high-quality aptamers. To date, however, there have been very few comprehensive studies exploring the relationship between aptamer binding properties and thermodynamics. Isothermal titration calorimetry (ITC) is a gold-standard method for studying the thermodynamics of ligand-receptor interactions. In this work, we have compiled ITC-derived thermodynamic binding data from 317 small-molecule-binding DNA aptamers, along with specificity profiles for ∼6000 aptamer-ligand pairs, and performed systematic analysis of the resulting datasets. This analysis revealed a variety of interesting patterns and trends. For example, ligand binding for most aptamers is generally driven solely by enthalpy, and aptamers with the highest binding enthalpy and greatest entropic binding penalties consistently have high specificity. We envision that the expansion and further analysis of such datasets will yield a far better understanding of the complex interplay between the various non-covalent interactions underlying aptamer-ligand recognition.
Alkhamis et al. (Thu,) studied this question.