Artificial Intelligence in Druggable Protein Identification: Data-driven Multidimensional Representations and the Evolution of Predictive Models.

Abstract

Druggable proteins are proteins that can be specifically bound and modulated by drug molecules, with such modulation expected to produce therapeutic effects. The identification and validation of druggable proteins are central steps in modern drug discovery. With the rapid advancements in biological big data and artificial intelligence, computational methods based on bioinformatics have become essential for large-scale screening of druggable proteins. This review systematically summarizes the latest research progress in this field, providing a comprehensive analysis across three dimensions: data resources, feature engineering, and predictive models. The main contributions are 4-fold: First, we systematically describe three major types of databases: pharmacological annotation databases, quantitative affinity databases, and multi-source integrated databases, and dataset construction strategies as well as strategies for handling imbalanced samples are explored. Second, multi-level feature representations across four dimensions are categorized into sequencederived features, physicochemical properties, evolutionary information, and structural information, and the corresponding methods and tools are summarized. Third, we provide a detailed review of the evolution and application paradigms of predictive models, from classical machine learning and ensemble learning to deep learning architectures and protein large language models. Fourth, based on a systematic evaluation of representative studies, current limitations in areas such as few-shot learning and model interpretability are highlighted, and offer a forward-looking perspective on future research directions. This review aims to serve as a comprehensive reference for druggable protein prediction algorithms and to provide a solid theoretical and technical roadmap for computationally driven discovery of novel drug targets.