Molecular Similarity： Methods and Performance

• Published in: Chinese journal of chemistry 2013-09, Vol.31 (9), p.1123-1132
• Main Authors: Cai, Chaoqian, Gong, Jiayu, Liu, Xiaofeng, Gao, Daqi, Li, Honglin
• Format: Article
• Language: English
• Subjects: Methods; molecular alignment; molecular modeling; molecular similarity; Proteins; Studies; virtual screening; 三维构象; 分子相互作用; 分子相似性; 定量测量; 性能; 结构检索; 蛋白质相互作用; 评价方法
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.201300390

Molecular similarity has long been a hot topic, which has been evaluated and compared by various approaches and plays a significant role in protein-ligand and protein-protein interactions recognition. There are currently many types of molecular similarity evaluation methods with their own advantages and disadvantages. Molecular finger- prints are the most common methods for molecular similarity evaluation which only concern about rapid 2D com- mon substructure retrieval but lack the ability to encode the information about 3D conformers. 3D molecular de- scriptor based methods bear the advantages of representing the structure information of a conformer, but the de- scriptors are not guaranteed to describe the molecules precisely. Molecular alignment based methods try to super- impose two molecules and evaluate the similarity using the optimal poses which are generally more precise than the molecular descriptor but require a time-consuming optimization process. Pharmacophore based methods only focus on the chemical features about a molecule and are not capable of dealing with the molecular shape similarity. In or- der to evaluate the performance of molecular similarity based screening, many kinds of metrics are available, e.g., visual representation, quantitative measurements and scaffold hopping ability measurements. Further applications of molecular similarity include construction of molecule interaction network or generation of diverse compounds li- brary.