Current progress, challenges, and future perspectives of language models for protein representation and protein design

The sequence-structure-function paradigm of protein is the basis of molecular biology. What is the underlying mechanism of such sequence and structure/function corresponding relationship? We reviewed the methods for protein representation and protein design. With these protein representation models, we can accurately predict many properties of proteins, such as stability and binding affinity. Progen, Chroma, RF Diffusion, SCUBA, and other protein design models have demonstrated how human-designed artificial proteins can have desired biological functions. The protein design will revolutionize drug development. And more efficient artificial enzymes that break down industrial waste or plastics will contribute to carbon neutrality. We also discussed the three greatest challenges of protein design in future and possible solutions.