Overview of AlphaFold2 and breakthroughs in overcoming its limitations

Abstract

Predicting three-dimensional (3D) protein structures has been challenging for decades. The emergence of AlphaFold2 (AF2), a deep learning-based machine learning method developed by DeepMind, became a game changer in the protein folding community. AF2 can predict a protein's three-dimensional structure with high confidence based on its amino acid sequence. Accurate prediction of protein structures can dramatically accelerate our understanding of biological mechanisms and provide a solid foundation for reliable drug design. Although AF2 breaks through the barriers in predicting protein structures, many rooms remain to be further studied. This review provides a brief historical overview of the development of protein structure prediction, covering template-based, template-free, and machine learning-based methods. In addition to reviewing the potential benefits (Pros) and considerations (Cons) of using AF2, this review summarizes the diverse applications, including protein structure predictions, dynamic changes, point mutation, integration of language model and experimental data, protein complex, and protein-peptide interaction. It underscores recent advancements in efficiency, reliability, and broad application of AF2. This comprehensive review offers valuable insights into the applications of AF2 and AF2-inspired AI methods in structural biology and its potential for clinically significant drug target discovery.