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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. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulation in explicit water for the binding of the benchmark barnase-barstar complex was carried out to investigate the effect polarization of interprotein hydrogen bonds on its binding free energy. Our study is based on the AMBER force field but with polarized atomic charges derived from fragment quantum mechanical calculation for the protein complex. The quantum-derived atomic charges include the effect of polarization of interprotein hydrogen bonds, which was absent in the standard force fields that were used in previous theoretical calculations of barnase-barstar binding energy. This study shows that this polarization effect impacts both the static (electronic) and dynamic interprotein electrostatic interactions and significantly lowers the free energy of the barnase-barstar complex. [ABSTRACT FROM AUTHOR]

Molecular dynamics simulation is carried out to investigate the enzyme dynamics of RNase A with the HIS48 in three different states (HIP48 (protonated), HID48 (deprotonated), and H48A mutant). Insights derived from the current theoretical study, combined with the available experimental observations, enabled us to provide a microscopic picture for the efficient enzyme dynamics. Specifically, in the "closed" state or HIP48, the N-terminal hinge loop is intact and the enzyme remains in a relatively stable conformation which is preferred for catalytic reaction. Deprotonation of HIS48 induces the denaturing of this hinge-loop into a 310-helix, causing it to break the original interaction network around the loop-1 and drive the partial unfolding of the N-terminal. The enhanced dynamic motion of the N-terminal helix facilitates the release of the catalytic product (the rate limiting step) and speeds up the overall catalytic process. The current study established that HIS49 acts as a modulator for the transformation of conformational states through the perturbing of hydrogen bond networks across loop-1, the N-terminal helix, and other residues nearby. Our study suggests that HIS48 may also serve to transport loop-1's kinetic energy to the reaction center. [ABSTRACT FROM AUTHOR]

MD simulation of the WW domain of PIN based on a dynamically adjusted polarized protein-specific force field from quantum fragment calculations is carried out in both wild and VAL22ALA mutant states. The result shows that the geometry of the Arg14-TYR23 hydrogen bond is conserved upon mutation of VAL22 to ALA. However, the electrostatic energy of this hydrogen bond in the mutant is found to be 0.6 kcal/mol weaker than in the wild state, in close agreement with the experimentally measured upper limit of 1.2 kcal/mol. Analysis shows that the weakened energy of this hydrogen bond in the mutant is due to its dynamically changed polarization resulting from an altered local electrostatic environment near the hydrogen bond which becomes more exposed to the solvent than in the wild. [ABSTRACT FROM AUTHOR]