Natural Language Processing Methods for the Study of Protein–Ligand Interactions
J.H. Michels, Ramya Bandarupalli, Amin Ahangar Akbari, Thái Hoàng Lê, Hong Xiao, Jing Li, Erik Hom
Abstract
Natural Language Processing (NLP) has revolutionized the way computers are used to study and interact with human languages and is increasingly influential in the study of protein and ligand binding, which is critical for drug discovery and development. This review examines how NLP techniques have been adapted to decode the "language" of proteins and small molecule ligands to predict protein-ligand interactions (PLIs). We discuss how methods such as long short-term memory (LSTM) networks, transformers, and attention mechanisms can leverage different protein and ligand data types to identify potential interaction patterns. Significant challenges are highlighted, including the scarcity of high-quality negative data, difficulties in interpreting model decisions, and sampling biases of existing datasets. We argue that focusing on improving data quality, enhancing model robustness, and fostering both collaboration and competition could catalyze future advances in machine-learning-based predictions of PLIs.