Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
Molecular Biotechnology Aims and scope Submit manuscript

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.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files.

References

  1. Johnson, W. L., France, D. C., Rentz, N. S., Cordell, W. T., & Walls, F. L. (2017). Sensing bacterial vibrations and early response to antibiotics with phase noise of a resonant crystal. Scientific Reports, 7(1), 12138.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rogers, K. R., Apostol, A., Madsen, S. J., & Spencer, C. W. (2001). Fiber optic biosensor for detection of DNA damage. Analytica Chimica Acta, 444(1), 51–60.

    Article  CAS  Google Scholar 

  3. Wang, J., Rivas, G., Fernandes, J. R., Lopez Paz, J. L., Jiang, M., & Waymire, R. (1998). Indicator-free electrochemical DNA hybridization biosensor. Analytica Chimica Acta, 375(3), 197–203.

    Article  CAS  Google Scholar 

  4. Zainuddin, N. H., Chee, H. Y., Ahmad, M. Z., Mahdi, M. A., Abu Bakar, M. H., & Yaacob, M. H. (2018). Sensitive Leptospira DNA detection using tapered optical fiber sensor. Journal of Biophotonics, 11(8), e201700363.

    Article  PubMed  Google Scholar 

  5. Pinheiro, A. V., Han, D., Shih, W. M., & Yan, H. (2011). Challenges and opportunities for structural DNA nanotechnology. Nature Nanotechnology, 6(12), 763–772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Noy, A., Artyukhin, A. B., & Misra, N. (2009). Bionanoelectronics with 1D materials. Materials Today, 12(9), 22–31.

    Article  Google Scholar 

  7. Cooper, C. S. (2001). Applications of microarray technology in breast cancer research. Breast Cancer Research, 3(3), 158.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Triche, T. J., Schofield, D., & Buckley, J. (2001). DNA microarrays in pediatric cancer. Cancer Journal (Sudbury, Mass.), 7(1), 2–15.

    CAS  PubMed  Google Scholar 

  9. Grouse, L. H., Munson, P. J., & Nelson, P. S. (2001). Sequence databases and microarrays as tools for identifying prostate cancer biomarkers. Urology, 57(4 Supplement 1), 154–159.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang, W., Du, Y., & Wang, M. L. (2015). Noninvasive glucose monitoring using saliva nano-biosensor. Sensing and Bio-Sensing Research, 4, 23–29.

    Article  Google Scholar 

  11. Zhang, W., Liu, Y., & Wang Ming, L. (2013). DNA-functionalized single-walled carbon nanotube-based sensor array for gas monitoring. Smart Structures and Systems, 12(1), 73–95.

    Article  Google Scholar 

  12. Mallikaratchy, P. (2017). Evolution of complex target SELEX to identify aptamers against mammalian cell-surface antigens. Molecules, 22(2), 215.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ban, C., Chung, S., Park, D.-S., & Shim, Y.-B. (2004). Detection of protein–DNA interaction with a DNA probe: Distinction between single-strand and double-strand DNA–protein interaction. Nucleic Acids Research, 32(13), e110–e110.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Leung, C.-H., Chan, D.S.-H., He, H.-Z., Cheng, Z., Yang, H., & Ma, D.-L. (2012). Luminescent detection of DNA-binding proteins. Nucleic Acids Research, 40(3), 941–955.

    Article  CAS  PubMed  Google Scholar 

  15. Li, J., & Lu, Y. (2000). A Highly sensitive and selective catalytic DNA biosensor for lead ions. Journal of the American Chemical Society, 122(42), 10466–10467.

    Article  CAS  Google Scholar 

  16. Zhang, Z., Hejesen, C., Kjelstrup, M. B., Birkedal, V., & Gothelf, K. V. (2014). A DNA-mediated homogeneous binding assay for proteins and small molecules. Journal of the American Chemical Society, 136(31), 11115–11120.

    Article  CAS  PubMed  Google Scholar 

  17. Paniel, N., Baudart, J., Hayat, A., & Barthelmebs, L. (2013). Aptasensor and genosensor methods for detection of microbes in real world samples. Methods (San Diego, Calif.)., 64(3), 229–240.

    Article  CAS  PubMed  Google Scholar 

  18. Niazi, J. H., Verma, S. K., Niazi, S., & Qureshi, A. (2015). In vitro HER2 protein-induced affinity dissociation of carbon nanotube-wrapped anti-HER2 aptamers for HER2 protein detection. The Analyst, 140(1), 243–249.

    Article  CAS  PubMed  Google Scholar 

  19. Gautam, V., Nimmanpipug, P., Zain, S. M., Rahman, N. A., & Lee, V. S. (2021). Molecular dynamics simulations in designing DARPins as phosphorylation-specific protein binders of ERK2. Molecules, 26(15), 4540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Vertika, G., Nadia Hanim, S., Wei Lim, C., Sharifuddin, M. Z., Noorsaadah Abd, R., Vannajan Sanghiran, L., & Anand, G. (2015) Computational Alanine Scanning Mutagenesis: Characterizing the hotspots of ILK-Ankyrin Repeat and PINCH1 Complex, in Proceedings of the 3rd International Conference on Computation for Science and Technology, Atlantis Press

  21. Xu, W., Amire-Brahimi, B., Xie, X.-J., Huang, L., & Ji, J.-Y. (2014). All-atomic molecular dynamic studies of human CDK8: Insight into the A-loop, point mutations and binding with its partner CycC. Computational Biology and Chemistry, 51, 1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Wang, L., Bao, Q.-C., Xu, X.-L., Jiang, F., Gu, K., Jiang, Z.-Y., Zhang, X.-J., Guo, X.-K., You, Q.-D., & Sun, H.-P. (2015). Discovery and identification of Cdc37-derived peptides targeting the Hsp90–Cdc37 protein–protein interaction. RSC Advances, 5(116), 96138–96145.

    Article  CAS  Google Scholar 

  23. Shi, S., Zhang, S., & Zhang, Q. (2015). Probing difference in binding modes of inhibitors to MDMX by molecular dynamics simulations and different free energy methods. PLoS ONE, 10(10), e0141409.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Chong, W. L., Zain, S. M., Rahman, N. A., Othman, R., Othman, S. B., Nimmanpipug, P., Tayapiwatana, C., & Lee, V. S. (2015) Exploration of residue binding energy of potential ankyrin for Dengue virus II from MD simulations, in 3rd International Conference on Computation for Science and Technology (ICCST-3), Atlantis Press

  25. Dubey, K. D., Tiwari, G., & Ojha, R. P. (2017). Targeting domain-III hinging of dengue envelope (DENV-2) protein by MD simulations, docking and free energy calculations. Journal of molecular modeling, 23(4), 102.

    Article  PubMed  Google Scholar 

  26. Zhang, L., & Sun, Y. (2014). Biomimetic design of platelet adhesion inhibitors to block integrin α2β1-collagen interactions: I. construction of an affinity binding model. Langmuir, 30(16), 4725–4733.

    Article  CAS  PubMed  Google Scholar 

  27. Ieong, P., Amaro, R. E., & Li, W. W. (2015). Molecular dynamics analysis of antibody recognition and escape by human H1N1 influenza hemagglutinin. Biophysical Journal, 108(11), 2704–2712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sun, Y., & Liu, Q. (2015). Differential structural dynamics and antigenicity of two similar influenza H5N1 virus HA-specific HLA-A* 0201-restricted CLT epitopes. RSC Advances, 5(3), 2318–2327.

    Article  CAS  Google Scholar 

  29. dos Santos Passos, C., Simões-Pires, C. A., Carrupt, P.-A., & Nurisso, A. (2016). Molecular dynamics of zinc-finger ubiquitin binding domains: A comparative study of histone deacetylase 6 and ubiquitin-specific protease 5. Journal of Biomolecular Structure and Dynamics, 34(12), 2581–2598.

    PubMed  Google Scholar 

  30. Wichapong, K., Alard, J.-E., Ortega-Gomez, A., Weber, C., Hackeng, T. M., Soehnlein, O., & Nicolaes, G. A. (2016). Structure-based design of peptidic inhibitors of the interaction between CC chemokine ligand 5 (CCL5) and human neutrophil peptides 1 (HNP1). Journal of medicinal chemistry, 59(9), 4289–4301.

    Article  CAS  PubMed  Google Scholar 

  31. Wichapong, K., Rohe, A., Platzer, C., Slynko, I., Erdmann, F., Schmidt, M., & Sippl, W. (2014). Application of docking and QM/MM-GBSA rescoring to screen for novel Myt1 kinase inhibitors. Journal of Chemical Information and Modeling, 54(3), 881–893.

    Article  CAS  PubMed  Google Scholar 

  32. Platania, C. B., Di Paola, L., Leggio, G. M., Romano, G. L., Drago, F., Salomone, S., & Bucolo, C. (2015). Molecular features of interaction between VEGFA and anti-angiogenic drugs used in retinal diseases: A computational approach. Frontiers in pharmacology, 6, 248.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Phanich, J., Rungrotmongkol, T., Kungwan, N., & Hannongbua, S. (2016). Role of R292K mutation in influenza H7N9 neuraminidase toward oseltamivir susceptibility: MD and MM/PB (GB) SA study. Journal of computer-aided molecular design, 30, 917–926.

    Article  CAS  PubMed  Google Scholar 

  34. Golyshev, V. M., Pyshnyi, D. V., & Lomzov, A. A. (2021). Calculation of energy for RNA/RNA and DNA/RNA duplex formation by molecular dynamics simulation. Molecular Biology, 55(6), 927–940.

    Article  CAS  Google Scholar 

  35. Yesudas, J. P., Blinov, N., Dew, S. K., & Kovalenko, A. (2015). Calculation of binding free energy of short double stranded oligonucleotides using MM/3D-RISM-KH approach. Journal of Molecular Liquids, 201, 68–76.

    Article  CAS  Google Scholar 

  36. Chaubey, A. K., Dubey, K. D., & Ojha, R. P. (2015). MD simulation of LNA-modified human telomeric G-quadruplexes: A free energy calculation. Medicinal Chemistry Research, 24(2), 753–763.

    Article  CAS  Google Scholar 

  37. Islam, B., Stadlbauer, P., Neidle, S., Haider, S., & Sponer, J. (2016). Can we execute reliable MM-PBSA free energy computations of relative stabilities of different guanine quadruplex folds? The Journal of Physical Chemistry B, 120(11), 2899–2912.

    Article  CAS  PubMed  Google Scholar 

  38. Misra, V. K., & Honig, B. (1996). The electrostatic contribution to the B to Z transition of DNA. Biochemistry, 35(4), 1115–1124.

    Article  CAS  PubMed  Google Scholar 

  39. Lee, Y.-K., Lee, J., Choi, J. H., & Seok, C. (2012). Contribution of counterion entropy to the salt-induced transition between B-DNA and Z-DNA. Bulletin of the Korean Chemical Society, 33(11), 3719–3726.

    Article  CAS  Google Scholar 

  40. Zhang, W., Du, Y., Cranford, S. W., & Wang, M. L. (2015). Biosensor design through molecular dynamics simulation. International Journal of Biotechnology and Bioengineering, 10(1), 10–14.

    Google Scholar 

  41. Jalili, S., Maddah, M., & Schofield, J. (2016). Molecular dynamics simulation and free energy analysis of the interaction of platinum-based anti-cancer drugs with DNA. Journal of Theoretical and Computational Chemistry, 15(06), 1650054.

    Article  CAS  Google Scholar 

  42. Jalili, S., & Maddah, M. (2017). Molecular dynamics simulation of the sliding of distamycin anticancer drug along DNA: Interactions and sequence selectivity. Journal of the Iranian Chemical Society, 14, 531–540.

    Article  CAS  Google Scholar 

  43. Kim, D.-H., Im, H., Jee, J.-G., Jang, S.-B., Yoon, H.-J., Kwon, A.-R., Kang, S.-M., & Lee, B.-J. (2014). β-Arm flexibility of HU from Staphylococcus aureus dictates the DNA-binding and recognition mechanism. Acta Crystallographica Section D: Biological Crystallography, 70(12), 3273–3289.

    Article  CAS  PubMed  Google Scholar 

  44. Chen, L., Zheng, Q.-C., & Zhang, H.-X. (2015). Insights into the effects of mutations on Cren7–DNA binding using molecular dynamics simulations and free energy calculations. Physical Chemistry Chemical Physics, 17(8), 5704–5711.

    Article  CAS  PubMed  Google Scholar 

  45. Ishida, H., & Matsumoto, A. (2016). Mechanism for verification of mismatched and homoduplex DNAs by nucleotides-bound MutS analyzed by molecular dynamics simulations. Proteins: Structure, Function, and Bioinformatics., 84(9), 1287–1303.

    Article  CAS  Google Scholar 

  46. Liu, C., Zhu, Y., & Tang, M. (2016). Theoretical studies on binding modes of copper-based nucleases with DNA. Journal of Molecular Graphics and Modelling, 64, 11–29.

    Article  CAS  PubMed  Google Scholar 

  47. Galindo-Murillo, R., & Cheatham, T. E., III. (2014). DNA binding dynamics and energetics of cobalt, nickel, and copper metallopeptides. ChemMedChem, 9(6), 1252–1259.

    Article  CAS  PubMed  Google Scholar 

  48. Sahoo, B. R., Dikhit, M. R., Bhoi, G. K., Maharana, J., Lenka, S. K., Dubey, P. K., & Tiwari, D. K. (2015). Understanding the distinguishable structural and functional features in zebrafish TLR3 and TLR22, and their binding modes with fish dsRNA viruses: An exploratory structural model analysis. Amino Acids, 47, 381–400.

    Article  CAS  PubMed  Google Scholar 

  49. Chang, S., Zhang, D.-W., Xu, L., Wan, H., Hou, T.-J., & Kong, R. (2016). Exploring the molecular basis of RNA recognition by the dimeric RNA-binding protein via molecular simulation methods. RNA biology, 13(11), 1133–1143.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Sim, S., Wang, P., Beyer, B. N., Cutrona, K. J., Radhakrishnan, M. L., & Elmore, D. E. (2017). Investigating the nucleic acid interactions of histone-derived antimicrobial peptides. FEBS letters, 591(5), 706–717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Arba, M., & Tjahjono, D. H. (2015). The binding modes of cationic porphyrin-anthraquinone hybrids to DNA duplexes: In silico study. Journal of Biomolecular Structure and Dynamics, 33(3), 657–665.

    Article  CAS  PubMed  Google Scholar 

  52. Arba, M., Kartasasmita, R. E., & Tjahjono, D. H. (2016). Molecular docking and dynamics simulations on the interaction of cationic porphyrin–anthraquinone hybrids with DNA G-quadruplexes. Journal of biomolecular Structure and Dynamics, 34(2), 427–438.

    Article  CAS  PubMed  Google Scholar 

  53. Hu, G., Ma, A., & Wang, J. (2017). Ligand selectivity mechanism and conformational changes in guanine riboswitch by molecular dynamics simulations and free energy calculations. Journal of Chemical Information and Modeling, 57(4), 918–928.

    Article  CAS  PubMed  Google Scholar 

  54. Tumbi, K. M., Nandekar, P. P., Shaikh, N., Kesharwani, S. S., & Sangamwar, A. T. (2014). Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds. Journal of Molecular Recognition, 27(3), 138–150.

    Article  CAS  PubMed  Google Scholar 

  55. Ootsubo, M., Shimizu, T., Tanaka, R., Sawabe, T., Tajima, K., Yoshimizu, M., Ezura, Y., Ezaki, T., & Oyaizu, H. (2002). Oligonucleotide probe for detecting Enterobacteriaceae by in situ hybridization. Journal of Applied Microbiology, 93(1), 60–68.

    Article  CAS  PubMed  Google Scholar 

  56. Case, D. A., Ben-Shalom, I. Y., Brozell, S. R., Cerutti, D. S., Cheatham, T. E., III., Cruzeiro, V. W. D., Darden, T. A., Duke, R. E., Ghoreishi, D., Giambasu, G., Giese, T. J., Gilson, M. K., Gohlke, H., Götz, A. W., Greenes, D., Harris, R., Homeyer, N., Huang, Y., Izadi, S., … Kollman, P. A. (2019). Amber 2019. University of California.

    Google Scholar 

  57. Srinivasan, J., Cheatham, T. E., Cieplak, P., Kollman, P. A., & Case, D. A. (1998). Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate−DNA Helices. Journal of the American Chemical Society, 120(37), 9401–9409.

    Article  CAS  Google Scholar 

  58. Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert opinion on drug discovery, 10(5), 449–461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sitkoff, D., Sharp, K. A., & Honig, B. (1994). Accurate calculation of hydration free energies using macroscopic solvent models. The Journal of Physical Chemistry, 98(7), 1978–1988.

    Article  CAS  Google Scholar 

  60. Gilson, M. K., & Honig, B. (1988). Calculation of the total electrostatic energy of a macromolecular system: Solvation energies, binding energies, and conformational analysis. Proteins: Structure, Function, and Bioinformatics., 4(1), 7–18.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was financially supported by Thailand Science Research and Innovation (TSRI) (grant no. MRG6280217), and National Research Council of Thailand (NRCT).

Author information

Authors and Affiliations

  1. Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla, 90110, Thailand

    Teerapong Pirojsirikul

  2. Department of Chemistry, Center of Theoretical and Computational Physics, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Vannajan Sanghiran Lee

  3. Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand

    Piyarat Nimmanpipug

Authors
  1. Teerapong Pirojsirikul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vannajan Sanghiran Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piyarat Nimmanpipug
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Teerapong Pirojsirikul.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pirojsirikul, T., Lee, V.S. & Nimmanpipug, P. Unraveling Bacterial Single-Stranded Sequence Specificities: Insights from Molecular Dynamics and MMPBSA Analysis of Oligonucleotide Probes. Mol Biotechnol 66, 582–591 (2024). https://doi.org/10.1007/s12033-024-01082-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12033-024-01082-0

Keywords

Search

Navigation