Decoding the effects of mutation on protein interactions using machine learning

Accurately predicting mutation-caused binding free energy changes (ΔΔGs) on protein interactions is crucial for understanding how genetic variations affect interactions between proteins and other biomolecules, such as proteins, DNA/RNA, and ligands, which are vital for regulating numerous biological processes. Developing computational approaches with high accuracy and efficiency is critical for elucidating the mechanisms underlying various diseases, identifying potential biomarkers for early diagnosis, and developing targeted therapies. This review provides a comprehensive overview of recent advancements in predicting the impact of mutations on protein interactions across different interaction types, which are central to understanding biological processes and disease mechanisms, including cancer. We summarize recent progress in predictive approaches, including physicochemical-based, machine learning, and deep learning methods, evaluating the strengths and limitations of each. Additionally, we discuss the challenges related to the limitations of mutational data, including biases, data quality, and dataset size, and explore the difficulties in developing accurate prediction tools for mutation-induced effects on protein interactions. Finally, we discuss future directions for advancing these computational tools, highlighting the capabilities of advancing technologies, such as artificial intelligence to drive significant improvements in mutational effects prediction.