Probing the interaction mechanism of tigecycline with γ-globulin and hemoglobin in the absence and presence of amikacin

• Published in: International journal of biological macromolecules 2025-02, Vol.291, p.139109, Article 139109
• Main Authors: Li, Xiangrong, Zhao, Jingjing, Liu, Xianfei, Song, Zhizhi, Xu, Wanqing, Li, Zheng
• Format: Article
• Language: English
• Subjects: Ternary system; The interaction mechanism; Tigecycline
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.139109

The interaction mechanism of tigecycline with γ-globulin and hemoglobin in the absence and presence of amikacin was investigated through multipectral, molecular docking and molecular dynamics simulation. The results show that tigecycline and γ-globulin/hemoglobin forms a ground state complex without or with amikacin. The presence of amikacin slightly increases the binding constant of tigecycline to γ-globulin/hemoglobin, but all are of moderate binding affinity, at 104 L mol−1. The equilibrium fraction of unbound tigecycline fu is >90 %, but the presence of amikacin reduces the free concentration of tigecycline in γ-globulin and hemoglobin. Whether amikacin is present or not, the interaction between tigecycline and γ-globulin/hemoglobin is a synergistic interaction driven by enthalpy and entropy. Non-covalent forces are primarily hydrophobic interactions, but also include electrostatic forces and hydrogen bonds. In the presence of amikacin, the effect of tigecycline on the skeleton structure of γ-globulin/hemoglobin is more significant. The effect of tigecycline and/or amikacin on the secondary structure of γ-globulin/hemoglobin is not significant, while the secondary structure changes in different systems are not the same. Molecular docking shows that γ-globulin/hemoglobin-tigecycline (first)-amikacin ternary system is the most stable. Molecular dynamics simulation explores the stability and dynamic behavior of γ-globulin/hemoglobin-tigecycline complex without or with amikacin. •The binding constant of tigecycline to both proteins increases because of amikacin.•The presence of amikacin reduces the free concentration of tigecycline.•The interaction between amikacin and the two proteins is non-spontaneous.•The secondary structure changes in different systems are not the same.•γ-Globulin/hemoglobin-tigecycline (first)-amikacin ternary system is the most stable.