Abstract: Studying the interaction between coal slime and flotation agents will be the hot and difficult point of flotation process strengthening. In view of the strong hydrophilic chemical structure characteristics of the surface of difficult flotation coal, this paper introduces the bio-pharmaceutical induced fit effect into the study of the interaction of polar collectors in difficult flotation coal flotation. In this paper, 3D coal molecular structure was optimized and constructed according to the results of coal sample properties. Protomol technology was used to search and represent the active pockets of coal molecules, and the optimal conformation of molecular butt between polar collector and difficult floating coal was searched in the active pockets. According to the binding energy of the optimal conformation of the interaction between polar chemicals and coal molecules, the correspondence between the molecular docking results, induced fit effect and the flotation results was analyzed. The molecular docking results and the recovery rates of refractory coal combustible are both lauryl alcohol< lauraldehyde< methyl laurate, The recovery rate of flotation fuels is positively correlated with the absolute value of molecular docking binding energy and the molecular induced binding effect of coal, which revealed the guiding effect of molecular docking on flotation reagent screening. According to the molecular docking configuration, the differences in binding energy can be attributed to the differences of π-CH interaction and steric hindrance. Furthermore, the three-dimensional space of pharmaceutical molecules was fixed and the induced fit effect between three polar collectors and coal molecules was explored by molecular mechanics simulation. It was found that methyl laurate and the active region of coal molecules could generate greater interaction, and the active region of coal molecules had stronger induction effect and inclusion of methyl laurate, so it had better effect in the flotation process. The application of molecular docking and induced fit effect technology in the field of biomedicine to the field of flotation reagents can provide technical approaches and scientific guidance for the rapid screening of flotation collectors.