Molecular dynamics study of DNA binding by INT-DBD under a polarized force field

Xue X. Yao, Chang G. Ji, Dai Q. Xie, John Zhang

Research output: Contribution to journalArticle

Abstract

The DNA binding domain of transposon Tn916 integrase (INT-DBD) binds to DNA target site by positioning the face of a three-stranded antiparallel β-sheet within the major groove. As the negatively charged DNA directly interacts with the positively charged residues (such as Arg and Lys) of INT-DBD, the electrostatic interaction is expected to play an important role in the dynamical stability of the protein-DNA binding complex. In the current work, the combined use of quantum-based polarized protein-specific charge (PPC) for protein and polarized nucleic acid-specific charge (PNC) for DNA were employed in molecular dynamics simulation to study the interaction dynamics between INT-DBD and DNA. Our study shows that the protein-DNA structure is stabilized by polarization and the calculated protein-DNA binding free energy is in good agreement with the experimental data. Furthermore, our study revealed a positive correlation between the measured binding energy difference in alanine mutation and the occupancy of the corresponding residue's hydrogen bond. This correlation relation directly relates the contribution of a specific residue to protein-DNA binding energy to the strength of the hydrogen bond formed between the specific residue and DNA.

Original languageEnglish (US)
Pages (from-to)1136-1142
Number of pages7
JournalJournal of Computational Chemistry
Volume34
Issue number13
DOIs
StatePublished - May 15 2013

Fingerprint

Force Field
Molecular Dynamics
Molecular dynamics
DNA
Binding Energy
Protein
Hydrogen Bonds
Proteins
DNA-Binding Proteins
Charge
Binding energy
Antiparallel
DNA-binding Protein
Hydrogen bonds
Interaction
Electrostatics
Molecular Dynamics Simulation
Integrases
Positioning
Free Energy

Keywords

  • binding energy
  • elestrostatic interaction
  • force field
  • hydrogen bond
  • PBSA
  • polarization
  • protein-DNA

ASJC Scopus subject areas

  • Chemistry(all)
  • Computational Mathematics

Cite this

Molecular dynamics study of DNA binding by INT-DBD under a polarized force field. / Yao, Xue X.; Ji, Chang G.; Xie, Dai Q.; Zhang, John.

In: Journal of Computational Chemistry, Vol. 34, No. 13, 15.05.2013, p. 1136-1142.

Research output: Contribution to journalArticle

Yao, Xue X. ; Ji, Chang G. ; Xie, Dai Q. ; Zhang, John. / Molecular dynamics study of DNA binding by INT-DBD under a polarized force field. In: Journal of Computational Chemistry. 2013 ; Vol. 34, No. 13. pp. 1136-1142.
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