Theoretical Analysis of Divalent Cation Effects on Aptamer Recognition of Neurotransmitter Targets

TL;DR

This paper uses molecular dynamics simulations to analyze how divalent cations like Mg2+ and Ca2+ influence aptamer conformations and recognition of neurotransmitters dopamine and serotonin, aiding biosensor design.

Contribution

It demonstrates the effectiveness of molecular dynamics simulations in predicting aptamer behavior and conformational changes influenced by divalent cations in biosensing environments.

Findings

Divalent cations significantly affect aptamer conformations.

Simulations correlate well with experimental data.

Molecular dynamics can predict aptamer-specific responses.

Abstract

Aptamer-based sensing of small molecules such as dopamine and serotonin in the brain, requires characterization of the specific aptamer sequences in solutions mimicking the in vivo environment with physiological ionic concentrations. In particular, divalent cations (Mg2+ and Ca2+) present in brain fluid, have been shown to affect the conformational dynamics of aptamers upon target recognition. Thus, for biosensors that transduce aptamer structure switching as the signal response, it is critical to interrogate the influence of divalent cations on each unique aptamer sequence. Herein, we demonstrate the potential of molecular dynamics simulations to predict the behaviour of dopamine and serotonin aptamers on sensor surfaces. The simulations enable molecular-level visualization of aptamer conformational changes that, in some cases, are significantly influenced by divalent cations. The correlations of theoretical simulations with experimental findings validate the potential for molecular dynamics simulations to predict aptamer-specific behaviors on biosensors