Computational Studies of a DNA-Based Aptasensor: toward Theory-Driven Transduction Improvement

Aptamers are a class of bioreceptors intensively used in current analytical tools dedicated to molecular diagnostics due to their ability to perform large structural reorganization upon target binding. However, there is a lack of methodologies allowing us to rationalize their structure in order to improve the transduction efficiency in aptamer sensors. We choose here, as a model system, a three-strand DNA structure as the probe, composed of two DNA strands anchored on a gold surface and partially hybridized with an aptamer sequence sensitive to ampicillin (AMP). The DNA structure has been designed to show strong structural change upon AMP binding to its aptamer. Using a set of computational techniques including molecular dynamics simulations, we deeply investigated the structure change upon analyte binding, taking into account the grafting on the surface. Original analyses of ion distributions along the trajectories unveil a distinct pattern between both states which can be related to changes in capacitance of the interface between these states. To our knowledge, this work demonstrates the ability of computational investigations for the first time to drive, in silico, the design of aptasensors.