DeepBSP—a Machine Learning Method for Accurate Prediction of Protein–Ligand Docking Structures

In recent years, machine-learning-based scoring functions have significantly improved the scoring power. However, many of these methods do not perform well in distinguishing the native structure from docked decoy poses due to the lack of decoy structural information in their training data. Here, we developed a machine-learning model, named DeepBSP, that can directly predict the root mean square deviation (rmsd) of a ligand docking pose with reference to its native binding pose. Unlike the binding affinity, the rmsd between the docking poses with reference to their native structures can be straightforwardly determined. By training on a generated data set with 11,925 native complexes and more than 165,000 docked poses, our model shows excellent docking power on our test set and also on the CASF-2016 docking decoy set compared to other major scoring functions. Thus, by combining molecular dockings that generate many poses with the application of DeepBSP, one can more accurately predict the best binding pose that is closest to the native complex structure. This DeepBSP model shall be very useful in picking out poses close to their natives from many poses generated from a dock application.