Evaluation of drug efficacy based on the spatial position comparison of drug–target interaction centers

The spatial position and interaction of drugs and their targets is the most important characteristics for understanding a drug’s pharmacological effect, and it could help both in finding new and more precise treatment targets for diseases and in exploring the targeting effects of the new drugs. In this work, we develop a computational pipeline to confirm the spatial interaction relationship of the drugs and their targets and compare the drugs’ efficacies based on the interaction centers. First, we produce a 100-sample set to reconstruct a stable docking model of the confirmed drug–target pairs. Second, we set 5.5 Å as the maximum distance threshold for the drug–amino acid residue atom interaction and construct 3-dimensional interaction surface models. Third, by calculating the spatial position of the 3-dimensional interaction surface center, we develop a comparison strategy for estimating the efficacy of different drug–target pairs. For the 1199 drug–target interactions of the 649 drugs and 355 targets, the drugs that have similar interaction center positions tend to have similar efficacies in disease treatment, especially in the analysis of the 37 targeted relationships between the 15 known anti-cancer drugs and 10 target molecules. Furthermore, the analysis of the unpaired anti-cancer drug and target molecules suggests that there is a potential application for discovering new drug actions using the sampling molecular docking and analyzing method. The comparison of the drug–target interaction center spatial position method better reflect the drug–target interaction situations and could support the discovery of new efficacies among the known anti-cancer drugs.