Bacterial resistance to β-lactam antibiotics pose a serious threat to human health. Penicillin binding proteins (PBPs) and β-lactamases are involved in both antibacterial activity and mediation of β-lactam antibiotic resistance. The two major reasons for resistance to β-lactams include: (i) pathogenic bacteria expressing drug insensitive PBPs rendering β-lactam antibiotics ineffective and (ii) production of β-lactamases along with alteration of their specificities. Thus, there is an urgent need to develop newer β-lactams to overcome the challenge of bacterial resistance. Therefore, the present study aims to identify the binding affinity of β-lactam antibiotics with different types of PBPs and β-lactamases. In this study, Cephalosporins and Carbapenems are docked in to PBP2a of Staphylococcus aureusand SHV-1β-lactamase of Escherichia coli. The results reveal that Ceftobiprole can efficiently bind to PBP2a and not strongly with SHV-1 β-lactamase. Furthermore, molecular dynamics (MD) simulations are performed to refine the binding mode of docked complex structure and to observe the differences in the stability of free PBP2a. MD simulation supports greater stability of Ceftobiprole-PBP2a complex compared to free PBP2a. This work demonstrates that potential β-lactam antibiotics can efficiently bind to different types of PBPs for circumventing β-lactam resistance and opens avenues for the development of newer antibiotics that can target bacterial pathogens.