ScFold: a GNN-based model for efficient inverse folding of short-chain proteins via spatial reduction.

Abstract

In the realm of protein design, the efficient construction of protein sequences that accurately fold into predefined structures has become an important area of research. Although advancements have been made in the study of long-chain proteins, the design of short-chain proteins requires equal consideration. The structural information inherent in short and single chains is typically less comprehensive than that of full-length chains, which can negatively impact their performance. To address this challenge, we introduce ScFold, a novel model that incorporates an innovative node module. This module utilizes spatial dimensionality reduction and positional encoding mechanisms to enhance the extraction of structural features. Experimental results indicate that ScFold achieves a recovery rate of 52.22$\%$ on the CATH4.2 dataset, demonstrating notable efficacy for short-chain proteins, with a recovery rate of 41.6$\%$. Additionally, ScFold further exhibits enhanced recovery rates of 59.32$\%$ and 61.59$\%$ on the TS50 and TS500 datasets, respectively, demonstrating its effectiveness across diverse protein types. Additionally, we performed protein length stratification on the TS500 and CATH4.2 datasets and tested ScFold on length-specific sub-datasets. The results confirm the model's superiority in handling short-chain proteins. Finally, we selected several protein sequence groups from the CATH4.2 dataset for structural visualization analysis and provided comparisons between the model-generated sequences and the target sequences.