College of Chemical Engineering, Sichuan University of Science and Engineering, Zigong City, Sichuan Province, 64300, China.
Digestive Department, Binhai New Area Hospital of TCM Tianjin, Tianjin, 300451, China.
Comput Biol Med. 2024 Jun;176:108620. doi: 10.1016/j.compbiomed.2024.108620. Epub 2024 May 15.
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.
预测三维(3D)蛋白质结构几十年来一直具有挑战性。由 DeepMind 开发的基于深度学习的机器学习方法 AlphaFold2(AF2)的出现,改变了蛋白质折叠领域的游戏规则。AF2 可以根据氨基酸序列高度自信地预测蛋白质的三维结构。准确预测蛋白质结构可以极大地加速我们对生物机制的理解,并为可靠的药物设计提供坚实的基础。尽管 AF2 在预测蛋白质结构方面取得了突破,但仍有许多问题需要进一步研究。
本文简要回顾了蛋白质结构预测的发展历史,涵盖基于模板、无模板和基于机器学习的方法。除了回顾使用 AF2 的潜在益处(Pros)和考虑因素(Cons)外,本文还总结了其在蛋白质结构预测、动态变化、点突变、语言模型和实验数据的整合、蛋白质复合物和蛋白质-肽相互作用等方面的多种应用。本文强调了 AF2 在效率、可靠性和广泛应用方面的最新进展。
本综述全面介绍了 AF2 在结构生物学中的应用以及受其启发的人工智能方法在临床上有意义的药物靶标发现方面的潜力,为相关研究提供了有价值的见解。
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