{"title":"Advancing protein structure prediction beyond AlphaFold2.","authors":"Sanggeun Park, Sojung Myung, Minkyung Baek","doi":"10.1016/j.sbi.2025.102985","DOIUrl":null,"url":null,"abstract":"<p><p>Accurate prediction of protein structures is essential for understanding their biological functions. The release of AlphaFold2 in 2021 marked a significant breakthrough, delivering unprecedented accuracy. However, challenges remain, particularly for proteins with limited evolutionary data or complex molecular interactions. This review explores efforts to enhance AlphaFold2's performance through advanced sequence search techniques and alternative approaches, including protein language models and frameworks that integrate diverse biomolecular interactions. We propose that future progress will depend on developing models grounded in fundamental physicochemical principles, offering more accurate and comprehensive predictions across a wider spectrum of biological systems.</p>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"90 ","pages":"102985"},"PeriodicalIF":6.1000,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in structural biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.sbi.2025.102985","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Accurate prediction of protein structures is essential for understanding their biological functions. The release of AlphaFold2 in 2021 marked a significant breakthrough, delivering unprecedented accuracy. However, challenges remain, particularly for proteins with limited evolutionary data or complex molecular interactions. This review explores efforts to enhance AlphaFold2's performance through advanced sequence search techniques and alternative approaches, including protein language models and frameworks that integrate diverse biomolecular interactions. We propose that future progress will depend on developing models grounded in fundamental physicochemical principles, offering more accurate and comprehensive predictions across a wider spectrum of biological systems.
期刊介绍：
Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed.
In COSB, we help the reader by providing in a systematic manner:
1. The views of experts on current advances in their field in a clear and readable form.
2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.
[...]
The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance.
-Folding and Binding-
Nucleic acids and their protein complexes-
Macromolecular Machines-
Theory and Simulation-
Sequences and Topology-
New constructs and expression of proteins-
Membranes-
Engineering and Design-
Carbohydrate-protein interactions and glycosylation-
Biophysical and molecular biological methods-
Multi-protein assemblies in signalling-
Catalysis and Regulation
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