Designing novel proteins with desired functions is crucial in biology and
chemistry. However, most existing work focus on protein sequence design,
leaving protein sequence and structure co-design underexplored. In this paper,
we propose GeoPro, a method to design protein backbone structure and sequence
jointly. Our motivation is that protein sequence and its backbone structure
constrain each other, and thus joint design of both can not only avoid
nonfolding and misfolding but also produce more diverse candidates with desired
functions. To this end, GeoPro is powered by an equivariant encoder for
three-dimensional (3D) backbone structure and a protein sequence decoder guided
by 3D geometry. Experimental results on two biologically significant
metalloprotein datasets, including $\beta$-lactamases and myoglobins, show that
our proposed GeoPro outperforms several strong baselines on most metrics.
Remarkably, our method discovers novel $\beta$-lactamases and myoglobins which
are not present in protein data bank (PDB) and UniProt. These proteins exhibit
stable folding and active site environments reminiscent of those of natural
proteins, demonstrating their excellent potential to be biologically
functional.

本研究论文提出了一种名为 GeoPro 的方法，用于联合设计蛋白质骨架结构和序列。该方法基于三维骨架结构的等变编码器和由三维几何图形指导的蛋白质序列解码器。实验证明，在两个重要的生物金属蛋白数据集上，GeoPro 在大多数度量标准上优于其他基准方法，能够发现在蛋白质数据库和 UniProt 中不存在的新型 $eta$- 内酰胺酶和肌红蛋白，表现出与天然蛋白类似的稳定折叠和活性位点环境，展示了其在生物功能方面的巨大潜力。