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How AlphaFold2 Predicts Conditionally Folding Regions Annotated in an Intrinsically Disordered Protein Database, IDEAL
SIMPLE SUMMARY: Intrinsically disordered regions (IDRs) in intrinsically disordered proteins (IDPs) play important roles in various biological processes by providing protein binding regions. The regions can adopt local structures upon binding to their interaction partners. An IDP database—IDEAL—has...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952413/ https://www.ncbi.nlm.nih.gov/pubmed/36829461 http://dx.doi.org/10.3390/biology12020182 |
Sumario: | SIMPLE SUMMARY: Intrinsically disordered regions (IDRs) in intrinsically disordered proteins (IDPs) play important roles in various biological processes by providing protein binding regions. The regions can adopt local structures upon binding to their interaction partners. An IDP database—IDEAL—has collected these conditionally binding regions as Protean Segments (ProSs). A recently developed program, called AlphaFold2 (AF2), accurately predicts structural domains in proteins. Because ProSs have the bilateral characteristics of IDRs and ordered regions, assessing AF2 models corresponding to ProSs is worthwhile. We classified ProSs into three classes: the excellent class agrees well with the AF2 models, the poor class agrees poorly, and the average class agrees between these two. The ProSs in the excellent class were characterized by some features similar to globular structures, whereas those in the poor class showed features of extended structures. The ProSs in the excellent class were further grouped into those with high prediction reliability (pLDDT) and those with a relatively low pLDDT and a small normalized radius of gyration. ABSTRACT: AlphaFold2 (AF2) is a protein structure prediction program which provides accurate models. In addition to predicting structural domains, AF2 assigns intrinsically disordered regions (IDRs) by identifying regions with low prediction reliability (pLDDT). Some regions in IDRs undergo disorder-to-order transition upon binding the interaction partner. Here we assessed model structures of AF2 based on the annotations in IDEAL, in which segments with disorder-to-order transition have been collected as Protean Segments (ProSs). We non-redundantly selected ProSs from IDEAL and classified them based on the root mean square deviation to the corresponding region of AF2 models. Statistical analysis identified 11 structural and sequential features, possibly contributing toward the prediction of ProS structures. These features were categorized into two groups: one that contained pLDDT and the other that contained normalized radius of gyration. The typical ProS structures in the former group comprise a long α helix or a whole or part of the structural domain and those in the latter group comprise a short α helix with terminal loops. |
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