Probing the Functional Topology of a pH-Dependent Triple Helix DNA Nanoswitch Family through Gaussian Accelerated MD Simulation

J Chem Inf Model. 2019 Jun 24;59(6):2746-2752. doi: 10.1021/acs.jcim.9b00133. Epub 2019 May 22.

Abstract

The topology of a pH-dependent triple helix DNA nanoswitch family has been characterized through simulative analysis to evaluate the efficiency of the switching mechanism varying the length of the loop connecting the two strands forming the double helix portion. In detail, the system is formed by a double helix made by two six base complementary sequences, connected by one loop having an increasing number of thymidines, namely 5, 7, or 9. The triplex-forming sequence made by six bases, connected to the double helix through a constant 25 base loop, interacts at pH 5.0 through Hoogsteen hydrogen bonds with one strand of the double helical region. We demonstrate, through molecular dynamics simulation, that the thymidine loop length exerts a fine regulatory role for the stability of the triple helix structure and is critical in modulating the switching mechanism triggered by the pH increase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry*
  • DNA / genetics
  • Hydrogen Bonding
  • Hydrogen-Ion Concentration
  • Molecular Dynamics Simulation*
  • Nanostructures / chemistry*
  • Normal Distribution
  • Nucleic Acid Conformation

Substances

  • triplex DNA
  • DNA