Comparative Analysis of the Interfaces Between Monomers in the Dimers of Bacterial Histone-Like HU Proteins by the MM-GBSA Method

This study aims to perform a comparative analysis of the interfaces between monomers in the dimers of bacterial histone-like DNA-binding proteins (HU proteins) and investigate the correlation between the thermal stability and the binding free energy of monomers in the dimers. The interfaces were analyzed using the PDBePISA server, and the binding free energy of monomers in the dimers (ΔGdim) was calculated by the MM-GBSA method based on a combination of molecular mechanics and the generalized Born equation. It was demonstrated that the increase in ΔGdim of the HU protein from the mycoplasma Spiroplasma melliferum (HUSpM) correlates well with the increase in the thermal stability. It was found that there is a correlation between the decrease in the thermal stability of mutant variants of HUSpM, which bear alanine substitutions at the interface between monomers in the dimer, and the calculated ΔGdim values for the corresponding mutants. The results of this study confirm the applicability of the MM-GBSA method to the prediction of the thermal stability of histone-like proteins and the effect of single amino acid substitutions at the interface between monomers on the thermal stability of mutant proteins.