De novo post-SELEX optimization of a G-quadruplex DNA aptamer binding to marine toxin gonyautoxin 1/4.

ABSTRACT: Ligand-binding aptamers obtained by SELEX (Systematic Evolution of Ligands by EXponential enrichment) often have low affinity or/and specificity, and post-SELEX optimization is usually needed. Due to experimental difficulty in determining three-dimensional (3D) structures of aptamer-ligand complexes, there are few structure-guided methods for rational post-SELEX optimization. Here, we employed a de novo optimization approach to engineer high-affinity variants for a G-quadruplex (GQ) aptamer (GO18-T-d) that specifically binds to marine toxin gonyautoxin 1/4 (GTX1/4). First, temperature-dependent modeling was carried out to predict the atomic structure of GO18-T-d. Then, to identify key bases for the optimization, spontaneous binding simulations were performed to reveal the complex structure

SUBMITTER: Song M 

PROVIDER: S-EPMC7689369 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature