The application discloses a
protein sequence design method based on biomolecular interaction domain enhancement, which comprises the following steps: inputting a
protein main chain skeleton three-dimensional coordinate information of a size of L*N*3 to be subjected to
sequence design; obtaining a
protein sequence in contact with a
biomolecule and an interaction domain interval; clustering the obtained sequence and taking a representative sequence of each cluster as a
training set; extracting three-dimensional structure, secondary structure,
solvent accessibility and
functional annotation feature representation of each training sample; using a LoRA
algorithm to fine-tune the last ten
transformer modules of a general multi-
modal protein
language model ESM3, and giving greater weight to the loss of a
mask residue located in the interaction domain interval; and inputting the
atomic coordinates of the protein main chain skeleton to be subjected to
sequence design into the trained model to obtain a target sequence. On the one hand, the application utilizes multi-
modal information of a large amount of proteins; and on the other hand, the application can generate a more robust and reasonable
functional protein sequence.