Research Information System
ISCIENCE, vol.26, no.4, 2023 (SCI-Expanded)
Three-dimensional structure and dynamics are essential for protein function. Ad-vancements in hydrogen-deuterium exchange (HDX) techniques enable probing protein dynamic information in physiologically relevant conditions. HDX-coupled mass spectrometry (HDX-MS) has been broadly applied in pharmaceutical indus-tries. However, it is challenging to obtain dynamics information at the single amino acid resolution and time consuming to perform the experiments and pro-cess the data. Here, we demonstrate the first deep learning model, artificial intel-ligence-based HDX (AI-HDX), that predicts intrinsic protein dynamics based on the protein sequence. It uncovers the protein structural dynamics by combining deep learning, experimental HDX, sequence alignment, and protein structure prediction. AI-HDX can be broadly applied to drug discovery, protein engineer-ing, and biomedical studies. As a demonstration, we elucidated receptor-binding domain structural dynamics as a potential mechanism of anti-severe acute respi-ratory syndrome coronavirus 2 (SARS-CoV-2) antibody efficacy and immune escape. AI-HDX fundamentally differs from the current AI tools for protein analysis and may transform protein design for various applications.