Machine learning models based on residue interaction network for ABCG2 transportable compounds recognition

As the one of the most important protein of placental transport of environmental substances, the identification of ABCG2 transport molecules is the key step for assessing the risk of placental exposure to environmental chemicals. Here, residue interaction network (RIN) was used to explore the difference of ABCG2 binding conformations between transportable and non-transportable compounds. The RIN were treated as a kind of special quantitative data of protein conformation, which not only reflected the changes of single amino acid conformation in protein, but also indicated the changes of distance and action type between amino acids. Based on the quantitative RIN, four machine learning algorithms were applied to establish the classification and recognition model for 1100 compounds with transported by ABCG2 potential. The random forest (RF) models constructed with RIN presented the best and satisfied predictive ability with an accuracy of training set of 0.97 and the test set of 0.96 respectively. In conclusion, the construction of residue interaction network provided a new perspective for the quantitative characterization of protein conformation and the establishment of prediction models for transporter molecular recognition. The ABCG2 transport molecular recognition model based on residue interaction network provides a possible way for screening environmental chemistry transported through placenta. [Display omitted] •ABCG2 as transporter expels environmental chemicals form placenta.•There were differences in the binding conformations of ABCG2 with various compounds.•RIN was used to quantify protein conformation.•QSAR models was used to identify ABCG2 transportable compounds.•Best model consists of RF and RIN descriptors. Synopsis statement:Residue interaction network provided an accurate and effective screening for environmental chemicals transported through placenta.