accurate reproduction of 161 small-molecule complex crystal structures using the eudoc program expanding the use of eudoc to supramolecular chemistry准确再生产161小分子复杂的晶体结构使用eudoc程序扩大使用eudoc超分子化学.pdfVIP

Accurate Reproduction of 161 Small-Molecule Complex Crystal Structures using the EUDOC Program: Expanding the Use of EUDOC to Supramolecular Chemistry Qi Wang, Yuan-Ping Pang* Computer-Aided Molecular Design Laboratory, Mayo Clinic, Rochester, Minnesota, United States of America EUDOC is a docking program that has successfully predicted small-molecule-bound protein complexes and identified drug leads from chemical databases. To expand the application of the EUDOC program to supramolecular chemistry, we tested its ability to reproduce crystal structures of small-molecule complexes. Of 161 selected crystal structures of small-molecule guest- host complexes, EUDOC reproduced all these crystal structures with guest structure mass-weighted root mean square ˚ deviations (mwRMSDs) of ,1.0 A relative to the corresponding crystal structures. In addition, the average interaction energy of these 161 guest-host complexes ( 250.1 kcal/mol) was found to be nearly half of that of 153 previously tested small-molecule- bound protein complexes (2108.5 kcal/mol), according to the interaction energies calculated by EUDOC. 31 of the 161 ˚ complexes could not be reproduced with mwRMSDs of ,1.0 A if neighboring hosts in the crystal structure of a guest-host complex were not included as part of the multimeric host system, whereas two of the 161 complexes could not be reproduced ˚ with mwRMSDs of ,1.0 A if water molecules were excluded from the host system. These results demonstrate the significant influence of crystal packing on small molecule complexation and suggest that EUDOC is able to predict small-molecule complexes and that it is useful for the design of new materials, molecular sensors, and multimeric inh