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通过人工智能对RNA和DNA结构预测的批判性评估:模仿游戏。

Critical Assessment of RNA and DNA Structure Predictions via Artificial Intelligence: The Imitation Game.

作者信息

Bergonzo Christina, Grishaev Alexander

机构信息

Biomolecular Measurement Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States.

Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850, United States.

出版信息

J Chem Inf Model. 2025 Apr 14;65(7):3544-3554. doi: 10.1021/acs.jcim.5c00245. Epub 2025 Mar 30.

Abstract

Computational predictions of biomolecular structure via artificial intelligence (AI) based approaches, as exemplified by AlphaFold software, have the potential to model of all life's biomolecules. We performed oligonucleotide structure prediction and gauged the accuracy of the AI-generated models via their agreement with experimental solution-state observables. We find parts of these models in good agreement with experimental data, and others falling short of the ground truth. The latter include internal or capping loops, noncanonical base pairings, and regions involving conformational flexibility, all essential for RNA folding, interactions, and function. We estimate root-mean-square (r.m.s.) errors in predicted nucleotide bond vector orientations ranging between 7° and 30°, with higher accuracies for simpler architectures of individual canonically paired helical stems. These mixed results highlight the necessity of experimental validation of AI-based oligonucleotide model predictions and their current tendency to mimic the training data set rather than reproduce the underlying reality.

摘要

通过基于人工智能(AI)的方法对生物分子结构进行计算预测,以AlphaFold软件为例,有潜力对所有生命的生物分子进行建模。我们进行了寡核苷酸结构预测,并通过与实验溶液状态观测值的一致性来评估人工智能生成模型的准确性。我们发现这些模型的部分内容与实验数据高度一致,而其他部分则与实际情况存在差距。后者包括内部或封端环、非经典碱基配对以及涉及构象灵活性的区域,所有这些对于RNA折叠、相互作用和功能都至关重要。我们估计预测的核苷酸键向量方向的均方根(r.m.s.)误差在7°至30°之间,对于单个经典配对螺旋茎的较简单结构具有更高的准确性。这些混合结果凸显了对基于人工智能的寡核苷酸模型预测进行实验验证的必要性,以及它们目前倾向于模仿训练数据集而非再现潜在现实的趋势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a783/12004532/6750c100b786/ci5c00245_0001.jpg

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