title: Molecular dynamics study of DNA binding by INT-DBD under a polarized force field.
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.
authors: Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry of MOE, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China.
authors: Xue X
authors: XX
authors: Yao
authors: Chang G
authors: CG
authors: Ji
authors: Dai Q
authors: DQ
authors: Xie
authors: John Z H
authors: JZ
authors: Zhang
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D019426:Integrases / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011789:Quantum Theory
chemical_list: D004247:DNA; D019426:Integrases