Exploring the Ligand-Protein Networks in Traditional Chinese Medicine: Current Databases, Methods and Applications

While the concept of “single component–single target” in drug discovery seems to have come to an end, “Multi-component–multi-target” is considered to be another promising way out in this field. The Traditional Chinese Medicine (TCM), which has thousands of years’ clinical application among China and other Asian countries, is the pioneer of the “Multi-component–multi-target” and network pharmacology. Hundreds of different components in a TCM prescription can cure the diseases or relieve the patients by modulating the network of potential therapeutic targets. Although there is no doubt of the efficacy, it is difficult to elucidate convincing underlying mechanism of TCM due to its complex composition and unclear pharmacology. Without thorough investigation of its potential targets and side effects, TCM is not able to generate large-scale medicinal benefits, especially in the days when scientific reductionism and quantification are dominant. The use of ligand-protein networks has been gaining significant value in the history of drug discovery while its application in TCM is still in its early stage. This article firstly surveys TCM databases for virtual screening that have been greatly expanded in size and data diversity in recent years. On that basis, different screening methods and strategies for identifying active ingredients and targets of TCM are outlined based on the amount of network information available, both on sides of ligand bioactivity and the protein structures. Furthermore, applications of successful in silico target identification attempts are discussed in details along with experiments in exploring the ligand-protein networks of TCM. Finally, it will be concluded that the prospective application of ligand-protein networks can be used not only to predict protein targets of a small molecule, but also to explore the mode of action of TCM.