In the following, we showcase the performance of ESP-Sim on a variety of benchmark tasks. We then perform a retrospective case study, where we aim to demonstrate the value of using shape and electrostatic similarities in scaffold-hopping exercises. Scaffold hopping is a method for identifying bioisosteric replacements with the intention of retaining biological activity of analog compounds but also improving other relevant molecular properties. It can also be used as a design strategy for intellectual property (IP) reasons.