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

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 f_u 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.