Knowledge-Design: Pushing the Limit of Protein Design via Knowledge Refinement
This work addresses limitations in protein design for computational biology by improving accuracy and efficiency, representing a strong specific gain rather than a foundational breakthrough.
The paper tackles the problem of protein design by proposing a knowledge-aware module to refine low-quality residues and a memory-retrieval mechanism to reduce training time, achieving a 9% improvement over the previous PiFold method and being the first to exceed 60% recovery on key benchmarks.
Recent studies have shown competitive performance in protein design that aims to find the amino acid sequence folding into the desired structure. However, most of them disregard the importance of predictive confidence, fail to cover the vast protein space, and do not incorporate common protein knowledge. After witnessing the great success of pretrained models on diverse protein-related tasks and the fact that recovery is highly correlated with confidence, we wonder whether this knowledge can push the limits of protein design further. As a solution, we propose a knowledge-aware module that refines low-quality residues. We also introduce a memory-retrieval mechanism to save more than 50\% of the training time. We extensively evaluate our proposed method on the CATH, TS50, and TS500 datasets and our results show that our Knowledge-Design method outperforms the previous PiFold method by approximately 9\% on the CATH dataset. Specifically, Knowledge-Design is the first method that achieves 60+\% recovery on CATH, TS50 and TS500 benchmarks. We also provide additional analysis to demonstrate the effectiveness of our proposed method. The code will be publicly available.