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The study of interactions between DNA and PcrA DNA helicase by using targeted molecular dynamic simulations

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Abstract

DNA helicases are important enzymes involved in all aspects of nucleic acid metabolism, ranging from DNA replication and repair to recombination, rescue of stalled replication and translation. DNA helicases are molecular motors. Through conformational changes caused by ATP hydrolysis and binding, they move along the template double helix, break the hydrogen bonds between the two strands and separate the template chains, so that the genetic information can be accessed. In this paper, targeted molecular dynamic simulations were performed to study the important interactions between DNA and PcrA DNA helicase, which can not be observed from the crystal structures. The key residues on PcrA DNA helicase that have strong interactions with both double stranded DNA (ds-DNA) and single stranded DNA (ss-DNA) have been identified, and it was found that such interactions mostly exist between the protein and DNA backbone, which indicates that the translocation of PcrA is independent of the DNA sequence. The simulations indicate that the ds-DNA is separated upon ATP rebinding, rather than ATP hydrolysis, which suggests that the two strokes in the mechanism have two different major roles. Firstly, in the power stroke (ATP hydrolysis), most of the translocations of the bases from one pocket to the next occur. In the relaxation stroke (ATP binding), most of the ‘work’ is being done to ‘melt’ the DNA at the separation fork. Therefore, we propose a mechanism whereby the translocation of the ss-DNA is powered by ATP hydrolysis and the separation of the ds-DNA is powered by ATP binding.

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Acknowledgments

This work was supported by the University of Nottingham; National Natural Science Foundation of China [81260481]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry [2013-693]; Chunhui Program, Ministry of Education of the People’s Republic of China [Z2011050]; Scientific Research Project for Ningxia Colleges and Universities, Department of Education of Ningxia [2011JY004] and University of Malaya-MOHE High Impact Research grant (UM.C/625/1/HIR/MOHE/DENT/22).

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Authors and Affiliations

  1. School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750004, People’s Republic of China

    Hao Wang & Jiajia Cui

  2. School of Chemistry and Chemical Engineering, Beifang University of Nationalities, Yinchuan, Ningxia, 750021, People’s Republic of China

    Wei Hong

  3. Dental Research and Training Unit and Oral Cancer Research Coordinating Centre, Faculty of Dentistry, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Ian C. Paterson

  4. School of Pharmacy and Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK

    Charles A. Laughton

Authors
  1. Hao Wang
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  2. Jiajia Cui
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  3. Wei Hong
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  4. Ian C. Paterson
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  5. Charles A. Laughton
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Correspondence to Hao Wang.

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Wang, H., Cui, J., Hong, W. et al. The study of interactions between DNA and PcrA DNA helicase by using targeted molecular dynamic simulations. J Mol Model 19, 4997–5006 (2013). https://doi.org/10.1007/s00894-013-2008-4

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  • DOI: https://doi.org/10.1007/s00894-013-2008-4

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