Assessment of AI-based Protein Structure Prediction for the NLRP3 Target
The recent success of AlphaFold and RoseTTAFold has demonstrated the values of AI methods in predicting highly accurate protein structures. Despite the advances, their roles in the context of small-molecule drug discovery need to be thoroughly explored. In this study, we evaluated the possibility whether the AI-based models can lead to reliable 3D structures of protein-ligand complexes. With the AI-generated protein structure, we were able to confidently predict the binding modes of small-molecule inhibitors for NLRP3, a challenging protein target in terms of obtaining the 3D model both experimentally and computationally. We therefore concluded that through careful evaluation, AI-predicted protein structures can be trusted and useful for small-molecule drug discovery projects.