Identification of novel multitargeted PPARa/?/d pan agonists by core hopping of rosiglitazone

Wang, Xue-Jiao; Zhang, Jun; Wang, Shu-Qing; Xu, Wei-Ren; Cheng, Xian-Chao; Wang, Run-Ling

The Core Hopping module in Schrodinger 2009 software was used to modify the polar head, linker, and hydrophobic tail of rosiglitazone ( Figure 2 ). 19 Core hopping is a docking algorithm that has the functions of fragment-based replacing and molecular docking. [20] [21] [22] The first step of core hopping was to define the points at which the cores were attached to the scaffold. It was performed in the Define Combinations Step from the Combinatorial Screening panel. The second step was to define "the receptor grid file", which was done in the Receptor Preparation panel. The third step was to prepare the cores attached to the scaffold using fragment database derived from ZINC. 23, 24 The fourth step was to align and dock the entire molecular structure built up by the core and scaffold. The cores were sorted and filtered by goodness of alignment and then redocked into the receptor after attaching the scaffold, followed by using the docking scores to sort the final molecules. [25] [26] [27] The original ligand AZ242, rosiglitazone, and TIPP204 were used as positive control compounds.