# AlphaFold Distillation for Protein Design

arXiv: https://arxiv.org/abs/2210.03488 · HTML: https://mlsanity.com/paper/2210.03488/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 9 of its 36 references that are in the map.
- First posted on arXiv 5 Oct 2022.

## Builds on (most cited first, 9 of 9)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Distilling the Knowledge in a Neural Network](https://mlsanity.com/paper/1503.02531/) (2015)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [Representing Long-Range Context for Graph Neural Networks with Global Attention](https://mlsanity.com/paper/2201.08821/) (2022)
- [ProtTrans: Towards Cracking the Language of Life's Code Through Self-Supervised Deep Learning and High Performance Computing](https://mlsanity.com/paper/2007.06225/) (2020)
- [Protein Representation Learning by Geometric Structure Pretraining](https://mlsanity.com/paper/2203.06125/) (2022)
- [Iterative Refinement Graph Neural Network for Antibody Sequence-Structure Co-design](https://mlsanity.com/paper/2110.04624/) (2021)
- [PiFold: Toward effective and efficient protein inverse folding](https://mlsanity.com/paper/2209.12643/) (2022)
- [Fold2Seq: A Joint Sequence(1D)-Fold(3D) Embedding-based Generative Model for Protein Design](https://mlsanity.com/paper/2106.13058/) (2021)

## Abstract (arXiv)

Inverse protein folding, the process of designing sequences that fold into a specific 3D structure, is crucial in bio-engineering and drug discovery. Traditional methods rely on experimentally resolved structures, but these cover only a small fraction of protein sequences. Forward folding models like AlphaFold offer a potential solution by accurately predicting structures from sequences. However, these models are too slow for integration into the optimization loop of inverse folding models during training. To address this, we propose using knowledge distillation on folding model confidence metrics, such as pTM or pLDDT scores, to create a faster and end-to-end differentiable distilled model. This model can then be used as a structure consistency regularizer in training the inverse folding model. Our technique is versatile and can be applied to other design tasks, such as sequence-based protein infilling. Experimental results show that our method outperforms non-regularized baselines, yielding up to 3% improvement in sequence recovery and up to 45% improvement in protein diversity while maintaining structural consistency in generated sequences. Code is available at https://github.com/IBM/AFDistill