The human touch: Utilizing AlphaFold 3 to analyze structures of endogenous metabolons

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Structure Pub Date : 2024-09-19 DOI:10.1016/j.str.2024.08.018

Toni K. Träger, Christian Tüting, Panagiotis L. Kastritis

引用次数: 0

Abstract

Computational structural biology aims to accurately predict biomolecular complexes with AlphaFold 3 spearheading the field. However, challenges loom for structural analysis, especially when complex assemblies such as the pyruvate dehydrogenase complex (PDHc), which catalyzes the link reaction in cellular respiration, are studied. PDHc subcomplexes are challenging to predict, particularly interactions involving weaker, lower-affinity subcomplexes. Supervised modeling, i.e., integrative structural biology, will continue to play a role in fine-tuning this type of prediction (e.g., removing clashes, rebuilding loops/disordered regions, and redocking interfaces). 3D analysis of endogenous metabolic complexes continues to require, in addition to AI, precise and multi-faceted interrogation methods.

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人情味利用 AlphaFold 3 分析内源性代谢物的结构

计算结构生物学旨在准确预测生物分子复合物，AlphaFold 3 是这一领域的先锋。然而，结构分析面临着挑战，尤其是在研究丙酮酸脱氢酶复合物（PDHc）等复杂复合物时，该复合物催化了细胞呼吸中的链接反应。PDHc 亚复合物的预测具有挑战性，尤其是涉及较弱、亲和力较低的亚复合物的相互作用。有监督的建模，即综合结构生物学，将继续在微调这类预测方面发挥作用（例如，消除冲突、重建环路/紊乱区域以及重新对接界面）。除了人工智能，内源代谢复合物的三维分析仍然需要精确和多方面的分析方法。

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

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.