NABP-BERT: NANOBODY®-antigen binding prediction based on bidirectional encoder representations from transformers...

Antibody-mediated immunity is crucial in the vertebrate immune system. Nanobodies, also known as VHH or single-domain antibodies (sdAbs), are emerging as promising alternatives to full-length antibodies due to their compact size, precise target selectivity, and stability. However, the limited availability of nanobodies (Nbs) for numerous antigens (Ags) presents a significant obstacle to their widespread application. Understanding the interactions between Nbs and Ags is essential for enhancing their binding affinities and specificities. Experimental identification of these interactions is often costly and time-intensive. To address this issue, we introduce NABP-BERT, a deep-learning model based on the BERT architecture, designed to predict NANOBODY®-Ag binding solely from sequence information. Furthermore, we have developed a general pretrained model with transfer capabilities suitable for protein-related tasks, including protein-protein interaction tasks. NABP-BERT focuses on the surrounding amino acid contexts and outperforms existing methods, achieving an AUROC of 0.986 and an AUPR of 0.985.