Investigation of Binding Affinity Between Prokaryotic Proteins (AHU-IHF) and DNAs: Steered Molecular Dynamics Approach.

The aim of this work is to investigate the binding affinity between the prokaryotic proteins-AHU-IHF proteins (AHU (AHU2, TR3, and AHU6) and IHF (IHF-WT and IHF-ßE44A))-and DNAs (DNA, H'-DNA, and H'44A-DNA) by using the steered molecular dynamics (SMD) simulation and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The gained results show that although the fluctuation of the pulling force yielded the change of the pulling work, the higher pulling work of the AHU/DNA complexes in comparison to those of the IHF/DNA complexes is not only dependent on the pulling force but also controlled by the change of the trajectory in SMD simulation process. In this study, the pulling work profile not only described the pulling pathway of the complexes but also reflected the hindered process of DNAs when AHU-IHF proteins come out from the binding pocket of DNAs. Additionally, the binding free energy (estimated by the MM-PBSA method) is more confident in giving a true effect to the experimental results in comparison to the pulling force and the pulling work values. These results have also shown a fact that the AHU/DNA complexes were more stable than the IHF/DNA complexes.

Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).

The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.