Molecular Interactions of β‐Lactamase Enzyme KPC2 and Carbapenem Antibiotics: Computational Chemistry and Artificial Intelligence Analysis

Abstract The development of drugs to combat disease is a constantly evolving issue of great importance to the entire population. Among this group of molecules, broad‐spectrum antibiotics stand out as the clinical choice of physicians. The family of carbapenems are broad‐spectrum antibiotics used to treat diseases caused by gram‐positive and gram‐negative bacteria that have developed resistance to multiple antibiotics through enzyme production. This research focuses on the characterization of carbapenem enzyme systems using computational chemistry at the level of force field, artificial intelligence, and density functional theory. The computational results on antibiotic molecular structures have been compared with experimental references from UV‐vis spectroscopy, demonstrating high accuracy of several hybrid functionals. For the β‐Lactamase enzyme KPC2, the computational models of FF and AI agreed with the folded structure reported by X‐ray diffraction. Finally, the catalytic site calculated by Docking where the carbapenems‐enzyme interaction takes place was also in agreement with experimental data using water as medium and even in weak acids such as ethanol or methanol. Overall, the above computational characterization provides an understanding of how accurate current computational methods are for understanding the origin of bacterial resistance to one of the latest generation antibiotic families.