Study On The Binding Pattern And QSAR Of Luciferase From Vibrio Qinghai By Five Antibiotics

Antibiotics for which a large number of antibiotics have been put into use in the medical industry,agriculture and animal husbandry industry in recent years will cause pollution to the aquatic environment and ultimately threaten human health due to their prolonged exposure to the environment.Due to their wide range of species and complex interaction mechanisms when mixed,it is difficult to predict and evaluate their toxicity through experiments.This paper studies the toxicity mechanism and ecological risk evaluation of enrofloxacin(ENR),Chlortetracycline(CTC),Trimethoprim(TMP),Chloramphenicol(CMP)and erythromycin(ETM)of the single and bivariate mixture of five antibiotics in the presence of Vibrio Vulnificus(Q67)by computer simulation.(1)The three-dimensional crystal structure of Q67 lucigenase was established by homology modeling technology.After optimized by molecular dynamics simulation,the amino acids in the allowed region in and subyllase diagrams were100%,and the proportions of the verification-3D amino acid score higher than 0.2were 91.48%and 91.98%,respectively.(2)By studying ligand-receptor binding patterns through molecular docking and molecular dynamics,the van der Waals force provided the most important contribution to the binding free energy of the five complex systems.Therefore,the dominant factor for the binding of antibiotics to luciferase was shape compensation.The face-to-face accumulation between the diazohexane structure outside the active pocket region and the indoles structure of Phe194 and Phe250 in the molecular structure was the main reason for the highest toxicity value of antibiotic ENR.In addition,hydrogen bond forces constrain the binding sites and conformations of small molecules to a certain extent and affect the binding free energy of the system.The Hormesis effect antibiotic ENR has a competitive binding relationship with the and subunits of luciferase.(3)The coefficient of determination R²(0.8172-0.9400)and root mean square deviation RMSP(0.1168-0.1545)of the ten models based on the toxicity values of antibiotic binary mixtures p EC₅₀and p EC₃₀at 4-12h exposure times indicate that the models have good internal stability and external predictive ability;the descriptors n DB,MATs2v,and Dipole moment indicates that the intra-molecular double bond structure,the van der Waals volume of the molecule,the geometric configuration of the molecule and the polar bonds within the molecule are the key molecular structural information affecting the toxicity of mixtures.The models Q12 and P12 have higher R²and lower RMSP than the CA/IC model indicating that the developed QSAR model has better predictive ability for binary mixture toxicity.(4)The entropy assessment of risk shows that the RQx(0.0055?0.5327)of the Yangtze River is less than 1 and more than 0.01,which belongs to the medium-low risk waters;while the RQx of surface water and Pearl River waters are both less than0.1,which belongs to the low-risk waters;the Haihe and Yellow Sea belong to the high-risk waters,whose main risk factors are TMP and ENR,respectively;in addition,the actual concentrations of ENR and CTC are in the waters of the Haihe.It is also at high risk.