SurfFold: a unified model for protein inverse folding by integrating surface and structural information.

motivationProteins play a crucial role in biological systems, and accurate protein sequence prediction is essential for applications such as drug discovery. Existing inverse folding models primarily rely on protein backbone structure information, overlooking the biochemical properties embedded in protein surface data that constrain its functionality, leading to limited prediction accuracy.

resultsWe propose a novel inverse folding framework, SurfFold, which integrates both protein backbone structure and surface information for sequence prediction. Additionally, it incorporates side-chain structural information and its interaction with surface information. Then, we introduce a Representation alignment module to better fuze structure and surface Representations. Experimental results demonstrate that SurfFold achieves state-of-the-art performance on the CATH4.2 dataset, and additional experiments validate the effectiveness of the proposed modules. Moreover, the homologous structure inverse folding experiment also demonstrates that SurfFold possesses excellent capability in homologous protein design. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/jiudizhengf/SurfFold.