Predicting synergy of lysozyme with antibiotics – an in silico analysis of interaction of Amoxicillin and Cephalexin with hen-egg lysozyme

Abstract

Lysozyme is the key enzyme of the innate immunity, more known because of the hydrolytic degradation of the peptoglycans. This is important for defense from bacteria and viruses, and also important for introducing this enzyme in drug discovery mechanisms. This in silico study aims to conduct deep research about the interaction of lysozyme with beta-lactams (amoxicillin and cephalexin) and to provide a basis for the hypothesis of synergistic antimicrobial effect. Molecular docking was done by a blind-docking protocol. Four complexes revealed significant results. Highest binding affinity was detected in the human lysozyme-cephalexin complex (-7.4 FEB). The binding of cephalexin was significantly stronger than that of amoxicillin. Comparative analysis of the sequences confirmed that subtle substitutions in contact spots LEU-PHE are the molecular basis for the higher affinity of human lysozyme binding. Strong binding of antibiotics to the catalytic gate of the enzyme reveals the possible transport complex formation, which can benefit the localization and better penetration of the antibiotics in bacterial cells.