The purpose of the present study is to evaluate the ability of ESMACS and TIES to estimate binding affinities of a set of 150 compounds to the ROS1 protein target. Like many protein kinases, the binding site of ROS1 is well structured, and the binding mode for the scaffold of the congeneric series is clearly defined in the crystal structure. Under such circumstances, it is reasonable to expect that good predictions can be achieved, although rotatable bonds in some of the compounds may pose a challenge for the conformational sampling and hence the convergence of the predictions.