The new scaffold as a building block was further optimized through the second core hopping process by replacing the core3 with various fragments by searching the fragment database. Interestingly, the best substitute core4 also contains the same glycine as the terminal fragment on the other side of Neo or ZINC01602230. Subsequently, a series of compound candidates modified from the Neo structure were generated, and then the top ten compounds with the best binding affinity computed by Glide5 program [39, 42] were listed in Fig. 3 .