Anti-3CLpro Molecular Design Based on the Model Constrained by Specific DTIs.

Computer-aided drug design and artificial intelligence-driven drug design have accelerated drug discovery. However, how to design effective drugs that have strong interaction ability with target proteins to further improve the efficacy of drugs in treating diseases remains a key issue. This paper proposes a new target-specific drug generative model 3CLpro2mol to generate new drug molecules, which uses features of drug-target interactions (DTIs) to constrain the correlation between the drug and the target protein. To obtain as many drug-target interaction features as possible from a small amount of data, a small molecule extraction strategy is proposed to ensure the diversity of small molecules in the training samples. To improve the efficiency and accuracy of the generative model, a TOP K sampling strategy is used to generate tokens, which can improve the rationality and diversity of the generated molecules. The experimental results show that the proposed model has the potential to generate small molecules that interact better with the target protein.