Inclusion of Receptor Flexibility in the DockThor Program through the Soft Docking Approach

The soft docking is a simple strategy to implicitly consider the receptor flexibility in docking methodology through the softening of the van der Waals potential of an energy function. In this work, we performed redocking and crossdocking studies on benchmarking sets using the softened version of the MMFF94S force field implemented in the DockThor program. In general, softening the van der Waals potential improved the pose prediction of the experimental binding mode for the investigated sets, resulting of an increase of up to 12% in some protein targets (e.g. aldose redutase). In crossdocking assays, the soft docking strategy used together with the ensemble docking approach led to promising results for proteins with high flexibility, such as aldose reductase. Furthermore, the use of a softened version of the DockThor scoring function for pose prediction did not affected the accuracy of our machine learning-based scoring functions for affinity prediction.