Computational methods for scaffold hopping

Drug discovery is an expensive and risky process. For a long time, researchers have developed several approaches to reducing failure during that process. Scaffold hopping is often used to find several compounds with different structures but similar biological activities. Thus, scaffold hopping has an important role in the field of drug design. This chapter introduces the principles and shows some successful cases of computational methods for scaffold hopping. We divided these methods into five categories according to principles including pharmacophore, similarity, fragment replacement, machine learning, and biological activity similarity. We also discuss the shortcomings of computational methods for scaffold hopping and look forward to their future development.