“Efficacy–Nature–Structure” Relationship of Traditional Chinese Medicine Based on Chemical Structural Data and Bioinformatics Analysis

[Image: see text] Traditional Chinese medicines (TCMs) have wide pharmacological activities, and the ingredients in individual TCMs determine their efficacies. To understand the “efficacy–nature–structure” relationship of TCM, compounds from 2444 kinds of herbs were collected, and the associations between family, structure, nature, and biological activities were mined and analyzed. Bernoulli Naïve Bayes profiling and a data analysis method were used to predict the targets of compounds. The results show that genetic material determined the representation of ingredients from herbs and the nature of TCMs and that the superior scaffolds of compounds of cold nature were 2-phenylochrotinone, anthraquinone, and coumarin, while the compounds of hot nature were cyclohexene. The results of the similarity analysis and distribution for molecular descriptors of compounds show that compounds associated with the same nature were similar and compounds associated with different natures occurred as a transition in part. As for integral compounds from 2-phenylochrotinone, anthraquinone, coumarin, and cyclohexene, the value of the shape index increased, indicating the transition of scaffolds from a spherical structure to a linear structure, with various molecular descriptors decreasing. Three medicines and three recipes prescribed based on “efficacy–nature–structure” had a higher survival rate in the clinic and provided powerful evidence for TCM principles. The research improves the understanding of the “efficacy–nature–structure” relationship and extends TCM applications.