Estimation of Bond Free Energy with Gmx_Mmpbsa in Ndm-1 Complexes

We report the values obtained for the binding free energies (ΔGbind) of the complexes: NDM-1-M25 (43.80 kcal/mol), NDM-1-M26 (12.71 kcal/mol), NDM-1-M35 (19.92 kcal/mol), NDM-1-M37 (2.46 kcal/mol) and the reference system NDM-1-Meropenem (-10.09 kcal/mol). These results are based on previous absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, docking, and molecular dynamics calculations performed on a small library of potential NDM-1 enzyme inhibitors reported in the literature. Subsequently, the selected systems were evaluated by the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) method using the gmx_MMPBSA software. The MMPBSA method has been widely adopted to estimate protein-ligand binding affinities due to its efficiency and high correlation with experimental data. The obtained results suggest that, unlike the reference complex, the studied ligands probably do not bind to the receptor under the simulation conditions, which is in significant agreement with experimental data.