Computer-Aided Drug Discovery for Undruggable Targets

Undruggable targets are those of therapeutical significance but challenging for conventional drug design approaches. Such targets often exhibit unique features, including highly dynamic structures, a lack of well-defined ligand-binding pockets, the presence of highly conserved active sites, and functional modulation by protein–protein interactions. Recent advances in computational simulations and artificial intelligence have revolutionized the drug design landscape, giving rise to innovative strategies for overcoming these obstacles. In this review, we highlight the latest progress in computational approaches for drug design against undruggable targets, present several successful case studies, and discuss…

• NN
  National Natural Science Foundation of China

  Awards: 22237002, T2321001, 22307002
• CP
  China Postdoctoral Science Foundation

  Award: 2023M740071
• DO
  Department of Science and Technology of Sichuan Province

  Award: 2024YFHZ0009
• CA
  Chinese Academy of Medical Sciences

  Award: 2021-I2M-5-014
• NK
  National Key Research and Development Program of China

  Award: 2022YFA130370