Qiuyu Fu made important contribution to this study.

Hong Lin, Xiaozhe Zhang, Li Liu, Qiuyu Fu, Chuanlong Zang, Yan Ding, Yang Su, Zhixue Xu, Sining He, Xiaoli Yang, Xiayun Wei, Haibin Mao, Yasong Cui, Yi Wei, Chuanzheng Zhou, Lilin Du, Niu Huang, Ning Zheng, Tao Wang, and Feng Rao

Abstract
FoxO1 is a conserved transcription factor involved in energy metabolism. It is tightly regulated by modifications on its mRNA and protein and responds to environmental nutrient signals. FoxO1 controls the transcription of downstream genes mediating metabolic regulation. Dysfunction of FoxO1 pathways results in several metabolic diseases, including diabetes, obesity, non-alcoholic fatty liver disease, and atherosclerosis. Here, we summarize the mechanism of FoxO1 regulation behind these diseases and FoxO1-related drug discoveries.

The ZGC Forum 2019 “ZGC International Frontier Science and Technology Achievements Exhibition” (中关村国际前沿科技成果展) was held from October 16th to 19th, 2019 in the ZGC Exhibition Center.
 
This exhibition focuses on the theme of “cutting-edge technology and future industries” and focuses on five areas: artificial intelligence and information technology, life sciences and biotechnology, intelligent manufacturing and high-end equipment, new materials and new energy, and cutting-edge science and technology. A total of 167 scientific and technological achievements from 116 units at home and abroad were displayed.
 
Dr. Yu Zhou and Nannan Hou participated in the exhibition on behalf of NIBS, and presented the project “Molecular Simulation and Innovative Drug Discovery”.

Brief introduction: Halogen bonds (XBs) are increasingly attracting attention in the field of structure-based drug design, limited utilization of XBs in structure-based drug design has stimulated efforts to develop more effective computational guidance. Here, we analyzed the binding-site water properties of crystal structures with characterized XBs between ligand halogen atoms and protein backbone carbonyls and, thus, found that halogen atoms involved in XBs frequently replace binding-site waters upon ligand binding. Moreover, we observed that the preferential directionality of XBs aligned well with the orientations of these replaced waters, and these replaced waters exhibited differential energetic characteristics. Combining with the geometrical characteristics of XBs, we proposed a practical strategy for rational drug design utilizing XBs. Then, we explored XBs between the scaffold of ibrutinib and its kinase target protein BTK based on the strategy, and the XBs were validated by systematic structure-activity relationship studies and free energy calculations. Our studies provided a practical approach for rational drug design utilizing XBs with protein backbone carbonyl groups.