@inproceedings{
zhu2024bridgeif,
title={Bridge-{IF}: Learning Inverse Protein Folding with Markov Bridges},
author={Yiheng Zhu and Jialu Wu and Qiuyi Li and Jiahuan Yan and Mingze Yin and Wei Wu and Mingyang Li and Jieping Ye and Zheng Wang and Jian Wu},
booktitle={The Thirty-eighth Annual Conference on Neural Information Processing Systems},
year={2024},
url={https://openreview.net/forum?id=Q8yfhrBBD8}
}
Inverse protein folding is a fundamental task in computational protein design, which aims to design protein sequences that fold into the desired backbone structures. While the development of machine learning algorithms for this task has seen significant success, the prevailing approaches, which predominantly employ a discriminative formulation, frequently encounter the error accumulation issue and often fail to capture the extensive variety of plausible sequences. To fill these gaps, we propose Bridge-IF, a generative diffusion bridge model for inverse folding, which is designed to learn the probabilistic dependency between the distributions of backbone structures and protein sequences. Specifically, we harness an expressive structure encoder to propose a discrete, informative prior derived from structures, and establish a Markov bridge to connect this prior with native sequences. During the inference stage, Bridge-IF progressively refines the prior sequence, culminating in a more plausible design. Moreover, we introduce a reparameterization perspective on Markov bridge models, from which we derive a simplified loss function that facilitates more effective training. We also modulate protein language models (PLMs) with structural conditions to precisely approximate the Markov bridge process, thereby significantly enhancing generation performance while maintaining parameter-efficient training. Extensive experiments on well-established benchmarks demonstrate that Bridge-IF predominantly surpasses existing baselines in sequence recovery and excels in the design of plausible proteins with high foldability. The code is available at https://github.com/violet-sto/Bridge-IF.
Bridge-IF: Learning Inverse Protein Folding with Markov Bridges
Yiheng Zhu Jialu Wu Qiuyi Li Jiahuan Yan Mingze Yin Wei Wu Mingyang Li Jieping Ye Zheng Wang Jian Wu