Missense3D: leveraging protein structures, including AlphaFold models, to understand the effect of missense variants.

IF 4.7 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Biology Pub Date : 2026-10-13 DOI:10.1016/j.jmb.2026.170066

Ifigenia Tsitsa, Gordon Hanna, Anja Conev, Suhail A Islam, Michael Je Sternberg, Alessia David

引用次数: 0

Abstract

The growing availability of 3D protein structures enables large-scale assessment of missense variants and their phenotypic impact. Missense3D, first developed in 2019, predicts the structural consequences of amino acid substitutions and provides mechanistic explanations by identifying features such as cavities, steric clashes and disrupted non-covalent bonds that may cause protein misfolding. The new Missense3D algorithm presented here accepts genomics, protein, and structural coordinates; models variants on both single proteins and protein-protein complexes using experimental and predicted structures, including AlphaFold models; performs automated sequence-structure mapping; and evaluates structural model quality before analysis. The Missense3D web server is freely available to all users, including commercial ones, at https://missense3d.bc.ic.ac.uk/~missense3d2/.

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Missense3D：利用蛋白质结构，包括AlphaFold模型，来了解错义变异的影响。

三维蛋白质结构的日益可用性使大规模评估错义变异及其表型影响成为可能。Missense3D于2019年首次开发，它预测了氨基酸取代的结构后果，并通过识别可能导致蛋白质错误折叠的空腔、空间冲突和被破坏的非共价键等特征，提供了机制解释。本文提出的新的Missense3D算法接受基因组学、蛋白质和结构坐标；使用实验和预测结构对单个蛋白质和蛋白质复合物的变异进行建模，包括AlphaFold模型；执行自动序列结构映射；并在分析前对结构模型质量进行评价。Missense3D web服务器免费提供给所有用户，包括商业用户，网址为https://missense3d.bc.ic.ac.uk/~missense3d2/。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.