Ab initio predictions for 3D structure and stability of single- and double-stranded DNAs in ion solutions

PLoS Comput Biol. 2022 Oct 19;18(10):e1010501. doi: 10.1371/journal.pcbi.1010501. eCollection 2022 Oct.

Abstract

The three-dimensional (3D) structure and stability of DNA are essential to understand/control their biological functions and aid the development of novel materials. In this work, we present a coarse-grained (CG) model for DNA based on the RNA CG model proposed by us, to predict 3D structures and stability for both dsDNA and ssDNA from the sequence. Combined with a Monte Carlo simulated annealing algorithm and CG force fields involving the sequence-dependent base-pairing/stacking interactions and an implicit electrostatic potential, the present model successfully folds 20 dsDNAs (≤52nt) and 20 ssDNAs (≤74nt) into the corresponding native-like structures just from their sequences, with an overall mean RMSD of 3.4Å from the experimental structures. For DNAs with various lengths and sequences, the present model can make reliable predictions on stability, e.g., for 27 dsDNAs with/without bulge/internal loops and 24 ssDNAs including pseudoknot, the mean deviation of predicted melting temperatures from the corresponding experimental data is only ~2.0°C. Furthermore, the model also quantificationally predicts the effects of monovalent or divalent ions on the structure stability of ssDNAs/dsDNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA*
  • DNA, Single-Stranded
  • Ions
  • Nucleic Acid Conformation
  • RNA* / chemistry

Substances

  • RNA
  • DNA
  • DNA, Single-Stranded
  • Ions

Grants and funding

This work was supported by the Grants from the National Science Foundation of China (11971367 to BGZ, and 11605125 to YZS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.