The ACE2 receptor plays a vital role not only in the SARS-CoV-induced epidemic but also in various other diseases, including cardiovascular diseases and ARDS. While studies have explored the interactions between ACE2 and SARS-CoV proteins, comprehensive research utilizing bioinformatic tools on the ACE2 protein has been lacking. The one aim of present study was to extensively analyze the regions of the ACE2 protein. After utilizing all bioinformatics tools especially G104 and L108 regions on ACE2 were come forward. The results of our analysis revealed that possible mutations or deletions in the G104 and L108 regions play a critical role in both the biological functioning and the determination of the chemical-physical properties of ACE2. Additionally, these regions were found to be more susceptible to mutations or deletions compared to other regions of the ACE2 protein. Notably, the randomly selected peptide, LQQNGSSVLS (100–109), which includes G104 and L108, exhibited a crucial role in binding the RBD of the spike protein, as supported by docking scores. Furthermore, both MDs and iMODs results provided evidence that G104 and L108 influence the dynamics of ACE2-spike complexes. This study is expected to offer a new perspective on the ACE2-SARS-CoV interaction and other research areas where ACE2 plays a significant role, such as biotechnology (protein engineering, enzyme optimization), medicine (RAS, pulmonary and cardiac diseases), and basic research (structural motifs, stabilizing protein folds, or facilitating important inter molecular contacts, protein’s proper structure and function).