Using molecular docking between organic chemicals and lipid membrane to revise the well known octanol–water partition coefficient of the mixture

The octanol–water partition coefficient of a mixture has been widely used to predict the baseline toxicity of non-polar narcotic chemical mixtures, since toxic effects are usually generated by multiple mixtures. However, it remains unclear whether the validity of log Kowmix can be demonstrated, because experimental methods cannot be used to determine this parameter. The invalidity and the further revision of log Kowmix were therefore studied by using molecular docking between non-polar narcotic chemicals and lipid membrane (Ebinding). The results show Ebinding is a feasible substitute parameter for log Kow because their relationship is linear. Based on a molecular docking and QSAR model, a new calculated method of log Kowmix   was proposed as follows: log(Kowmix)=∑xi log Kowilog(Kowmix)=∑xi log Kowi. Comparison of this new method with the established methods demonstrates the invalidity of the latter, and therefore the former is suggested to be used to calculate the log Kowmix of organic chemical mixtures.

► Ebinding is demonstrated as the feasible parameter instead of log Kow. ► The QSAR model based on the Ebinding was proposed to predict baseline toxicity. ► The calculated method of log Kowmix was proposed. ► The proposed calculated method in our study was suggested to calculate the Kowmix.