AFflecto: A web server to generate conformational ensembles of flexible proteins from AlphaFold models.

IF 4.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Biology Pub Date : 2025-02-13 DOI:10.1016/j.jmb.2025.169003

Mátyás Pajkos, Ilinka Clerc, Christophe Zanon, Pau Bernadó, Juan Cortés

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引用次数: 0

Abstract

Intrinsically disordered proteins and regions (IDPs/IDRs) leverage their structural flexibility to fulfill essential cellular functions, with dysfunctions often linked to severe diseases. However, the relationships between their sequences, structural dynamics and functional roles remain poorly understood. Understanding these complex relationships is crucial for therapeutic development, highlighting the need for methods to generate plausible IDP/IDR conformational ensembles. While AlphaFold (AF) excels at modeling structured domains, it fails to accurately represent disordered regions, leaving a significant portion of proteomes inaccurately modeled. We present AFflecto, a user-friendly web server for generating large conformational ensembles of proteins that include both structured domains and IDRs from AF structural models. AFflecto identifies IDRs as tails, linkers or loops by analyzing their structural context. Additionally, it incorporates a method to identify conditionally folded IDRs that AF may incorrectly predict as natively folded elements. The conformational space is globally explored using efficient stochastic sampling algorithms. AFflecto's web interface allows users to customize the modeling, by modifying boundaries between ordered and disordered regions, and selecting among several sampling strategies. The web server is freely available at https://moma.laas.fr/applications/AFflecto/.

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来源期刊

Journal of Molecular Biology 生物-生化与分子生物学

CiteScore

11.30

自引率

1.80%

发文量

412

审稿时长

28 days

期刊介绍： Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions. Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.