The invention discloses a
protein sequence design method based on biomolecular interaction structural domain enhancement. The method comprises the following steps: firstly, inputting three-dimensional coordinate information of a
protein main chain skeleton to be subjected to
sequence design, wherein the size of the
protein main chain skeleton is L * N * 3; obtaining a protein sequence in contact with the biomolecules and an interaction structural domain interval; clustering the obtained sequences and taking out a representative sequence of each cluster as a
training set; extracting a three-dimensional structure, a secondary structure,
solvent accessibility and function
annotation feature representation of each training sample; fine-tuning the last ten
layers of
transformer modules of the universal multi-
modal protein
language model ESM3 by using an LoRA
algorithm, and giving a larger weight for the loss of
mask residues located in an interaction structural domain interval; and inputting
atomic coordinates of a protein main chain skeleton to be subjected to
sequence design into the trained model to obtain a target sequence. On one hand, multi-
modal information of massive proteins is utilized; on the other hand, a more robust and reasonable
functional protein sequence can be generated.