Structural characterization of the saxitoxin-targeting APTSTX1 aptamer using optical tweezers and molecular dynamics simulations

PLoS One. 2019 Nov 7;14(11):e0222468. doi: 10.1371/journal.pone.0222468. eCollection 2019.

Abstract

Optical tweezers have enabled the exploration of picoNewton forces and dynamics in single-molecule systems such as DNA and molecular motors. In this work, we used optical tweezers to study the folding/unfolding dynamics of the APTSTX1-aptamer, a single-stranded DNA molecule with high affinity for saxitoxin (STX), a lethal neurotoxin. By measuring the transition force during (un)folding processes, we were able to characterize and distinguish the conformational changes of this aptamer in the presence of magnesium ions and toxin. This work was supported by molecular dynamics (MD) simulations to propose an unfolding mechanism of the aptamer-Mg+2 complex. Our results are a step towards the development of new aptamer-based STX sensors that are potentially cheaper and more sensitive than current alternatives.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • DNA, Single-Stranded / chemistry*
  • Molecular Dynamics Simulation
  • Nanotechnology / methods
  • Neurotoxins / chemistry
  • Optical Tweezers
  • Saxitoxin / chemistry*

Substances

  • Aptamers, Nucleotide
  • DNA, Single-Stranded
  • Neurotoxins
  • Saxitoxin

Grants and funding

This work was supported by: FONDECYT 11130263 and 1181361, PCI PII20150073 U-INICIA Vicerrectoría de Investigación, Universidad de Chile (C.A.M.W.); Newton Picarte PCI-DPI-Conicyt 20140080, ICM P10-035F, Anillo ACT-1108 (N.P.B.). P.C. acknowledges support from Conicyt grants FONDECYT 11110050 and FONDEF ID18I10147. J.R.M. acknowledges support from Conicyt-Fondecyt grant number 1180673, Air Force Office of Scientific Research award numbers FA9550-18-1-0438 and FA9550-18-1-0513, and Office of Naval Research grant number N62909-18-1-2180.