{"title":"Bias in, bias out – AlphaFold-Multimer and the structural complexity of protein interfaces","authors":"Joelle Morgan Strom, Katja Luck","doi":"10.1016/j.sbi.2025.103002","DOIUrl":null,"url":null,"abstract":"<div><div>A structural understanding of protein–protein interactions is a key component of many facets of applied molecular biology research. AlphaFold-Multimer (AF-MM) provided a breakthrough in the ability to predict protein–protein interface structure. However, the available training data for this model and the resulting benchmarking and validation efforts show a bias toward interactions between more ordered regions of proteins. Here we highlight some of the successes and limitations of AF-MM and discuss available methods and future directions to enable balanced prediction of all interface types.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"91 ","pages":"Article 103002"},"PeriodicalIF":6.1000,"publicationDate":"2025-02-12","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://www.sciencedirect.com/science/article/pii/S0959440X2500020X","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
A structural understanding of protein–protein interactions is a key component of many facets of applied molecular biology research. AlphaFold-Multimer (AF-MM) provided a breakthrough in the ability to predict protein–protein interface structure. However, the available training data for this model and the resulting benchmarking and validation efforts show a bias toward interactions between more ordered regions of proteins. Here we highlight some of the successes and limitations of AF-MM and discuss available methods and future directions to enable balanced prediction of all interface types.
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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