Unraveling Bacterial Single-Stranded Sequence Specificities: Insights from Molecular Dynamics and MMPBSA Analysis of Oligonucleotide Probes

Mol Biotechnol. 2024 Apr;66(4):582-591. doi: 10.1007/s12033-024-01082-0. Epub 2024 Feb 19.

Abstract

We utilized molecular dynamics (MD) simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) free energy calculations to investigate the specificity of two oligonucleotide probes, namely probe B and probe D, in detecting single-stranded DNA (ssDNA) within three bacteria families: Enterobacteriaceae, Pasteurellaceae, and Vibrionaceae. Due to the limited understanding of molecular mechanisms in the previous research, we have extended the discussion to focus specifically on investigating the binding process of bacteria-probe DNA duplexes, with an emphasis on analyzing the binding free energy. The role of electrostatic contributions in the specificity between the oligonucleotide probes and the bacterial ssDNAs was investigated and found to be crucial. Our calculations yielded results that were highly consistent with the experimental data. Through our study, we have successfully exhibited the benefits of utilizing in-silico approaches as a powerful virtual-screening tool, particularly in research areas that demand a thorough comprehension of molecular interactions.

Keywords: Binding free energy; Electrostatics; Enterobacteriaceae; MMPBSA; Molecular dynamics; Oligonucleotide probe; Pasteurellaceae; Specificity; Vibrionaceae.

Publication types

  • Review

MeSH terms

  • DNA, Bacterial / genetics
  • DNA, Single-Stranded* / chemistry
  • DNA, Single-Stranded* / genetics
  • DNA, Single-Stranded* / metabolism
  • Molecular Dynamics Simulation*
  • Nucleic Acid Conformation
  • Oligonucleotide Probes* / chemistry
  • Oligonucleotide Probes* / genetics
  • Static Electricity
  • Thermodynamics

Substances

  • DNA, Single-Stranded
  • Oligonucleotide Probes
  • DNA, Bacterial