Study of Structure-active Relationship for Inhibitors of HIV-1 Integrase LEDGF/p75 Interaction by Machine Learning Methods

HIV-1 integrase (IN) is a promising target for anti-AIDS therapy, and LEDGF/p75 is proved to enhance the HIV-1 integrase strand transfer activity invitro. Blocking the interaction between IN and LEDGF/p75 is an effective way to inhibit HIV replication infection. In this work, 274 LEDGF/p75-IN inhibitors were collected as the dataset. Support Vector Machine (SVM), Decision Tree (DT), Function Tree (FT) and Random Forest (RF) were applied to build several computational models for predicting whether a compound is an active or weakly active LEDGF/p75-IN inhibitor. Each compound is represented by MACCS fingerprints and CORINA Symphony descriptors. The prediction accuracies for the test sets of all the models are over 70%. The best model Model 3B built by FT obtained a prediction accuracy and a Matthews Correlation Coefficient (MCC) of 81.08% and 0.62 on test set, respectively. We found that the hydrogen bond and hydrophobic interactions are important for the bioactivity of an inhibitor.