Staphylococcus aureus is a gram-positive bacterium known to cause mild to severe and potentially fatal infections such as endocarditis, sepsis, meningitis, pneumonia, and bacteremia, among others. The methicillin-resistant strain of Staphylococcus aureus (MRSA) arose because the bacterium acquired an additional penicillin-binding protein by lateral gene transfer, known as penicillin-binding protein 2a (PBP2a). It is responsible for cross-linking peptidoglycan chains in forming the bacterial cell wall. According to The Lancet, MRSA was the deadliest pathogen and drug combination globally in 2019, with 121,000 deaths attributable to antimicrobial resistance. For this reason, the need for developing new PBP2a inhibitors and treating the infections caused by this bacterium is vital. In this work, a systematic study of molecular docking and molecular dynamics was carried out for a series of aza-heterocyclic compounds against PBP2a in order to determine their stability and behavior of the complex over time under physiological conditions through root mean square deviation (RMSD) and the residence of interactions by hydrogen bonds. Additionally, the binding free energy was calculated to estimate the affinity between the ligand and protein, using the MM/GBSA method, obtaining promising results concerning the co-crystallized ligand used as a reference. In addition, the pharmacokinetic properties are discussed showing promising results.