Randomized controlled trials do not always fit the purpose: A science-based response to Venetis and Mol’s editorial on biosimilars of follitropin alfa

As major forces for modulating protein folding and molecular recognition, cation and π interactions are extensively identified in protein structures. They are even more competitive than hydrogen bonds in molecular recognition, thus, are vital in numerous biological processes. In this review, we introduce the methods for the identification and quantification of cation and π interactions, provide insights into the characteristics of cation and π interactions in the natural state, and reveal their biological function together with our developed database (Cation and π Interaction in Protein Data Bank; CIPDB; http://chemyang.ccnu.edu.cn/ccb/database/CIPDB). This review lays the foundation for the in-depth study of cation and π interactions and will guide the use of molecular design for drug discovery.