Papers › Knowledge-Design: Pushing the Limit of Protein Design via Knowledge Refinement
Knowledge-Design: Pushing the Limit of Protein Design via Knowledge Refinement
Zhangyang Gao, Cheng Tan, Stan Z. Li
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.
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Code
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Tasks
Results from the paper archive 2025-07-28
| Task | Dataset | Model | Metric | Value | Rank at snapshot | Leaderboard | Report |
|---|---|---|---|---|---|---|---|
| Protein Design | CATH 4.2 | Knowledge-Design | Perplexity | 3.46 | #1 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | Knowledge-Design | Sequence Recovery %(All) | 60.77 | #1 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | PiFold | Perplexity | 4.55 | #2 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | PiFold | Sequence Recovery %(All) | 51.66 | #2 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | ProteinMPNN | Perplexity | 4.61 | #3 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | ProteinMPNN | Sequence Recovery %(All) | 45.96 | #3 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GVP | Perplexity | 5.36 | #4 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GVP | Sequence Recovery %(All) | 39.47 | #4 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GCA | Perplexity | 6.05 | #5 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GCA | Sequence Recovery %(All) | 37.64 | #5 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | AlphaDesign | Perplexity | 6.3 | #6 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | AlphaDesign | Sequence Recovery %(All) | 41.31 | #6 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | StructGNN | Perplexity | 6.4 | #7 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | StructGNN | Sequence Recovery %(All) | 35.91 | #7 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GraphTrans | Perplexity | 6.63 | #8 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.2 | GraphTrans | Sequence Recovery %(All) | 35.82 | #8 of 8 | Archive leaderboard | report |
| Protein Design | CATH 4.3 | GVP-large | Perplexity | 6.17 | #1 of 2 | Archive leaderboard | report |
| Protein Design | CATH 4.3 | GVP-large | Sequence Recovery %(All) | 39.2 | #1 of 2 | Archive leaderboard | report |
| Protein Design | CATH 4.3 | ESM-IF | Perplexity | 6.44 | #2 of 2 | Archive leaderboard | report |
| Protein Design | CATH 4.3 | ESM-IF | Sequence Recovery %(All) | 38.3 | #2 of 2 | Archive leaderboard | report |
| Word Sense Disambiguation | TS50 | SPIN | Sequence Recovery %(All) | 30.3 | #1 of 1 | Archive leaderboard | report |
Ranks are positions in the archive's leaderboards as they stood at the 2025-07-28 snapshot. Results published since then are not among these rows, so a rank here is not a current standing.
Methods
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