DPAM : A domain parser for AlphaFold models
DPAM : A domain parser for AlphaFold models
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DPAM：AlphaFold 模型的域解析器
DOI：
10.1002/pro.4548
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发表时间：
2023
期刊：
影响因子：
8
通讯作者：
Grishin, Nick V.
中科院分区：
文献类型：
--
作者：
Zhang, Jing;Schaeffer, R. Dustin;Durham, Jesse;Cong, Qian;Grishin, Nick V.
最近结构预测方面的突破，诸如 AlphaFold 等方法证明了接近原子的准确性，预示着结构生物学的范式转变。 AlphaFold 数据库中发布的 2 亿个高精度模型预计将在未来几十年内指导蛋白质科学。将这些 AlphaFold 模型划分为多个域并将它们分配到进化层次结构中，提供了一种获得蛋白质功能洞察的有效方法。然而，对如此大量的预测结构进行分类对当前结构分类的基础设施提出了挑战，包括我们的蛋白质结构域进化分类（ECOD）。迫切需要更好的计算工具来自动解析和分类 AlphaFold 模型中的域。在这里，我们提出了一个用于 AlphaFold 模型的域解析器 (DPAM)，它可以根据 3D 结构中的残基间距离、预测的对齐错误以及通过序列 (HHsuite) 和结构 (Dali) 相似性搜索找到的 ECOD 域自动识别这些模型中的球状域。基于 18,759 个 AlphaFold 模型的基准，我们证明 DPAM 可以识别 98.8% 的域，并为 87.5% 分配正确的边界，显着优于基于结构的域解析器和使用 HHsuite 或 Dali 发现的 ECOD 域的基于同源性的域分配。将 DPAM 应用于大规模 AlphaFold 模型将能够实现领域的有效分类，提供进化背景并促进功能研究。
The recent breakthroughs in structure prediction, where methods such as AlphaFold demonstrated near‐atomic accuracy, herald a paradigm shift in structural biology. The 200 million high‐accuracy models released in the AlphaFold Database are expected to guide protein science in the coming decades. Partitioning these AlphaFold models into domains and assigning them to an evolutionary hierarchy provide an efficient way to gain functional insights into proteins. However, classifying such a large number of predicted structures challenges the infrastructure of current structure classifications, including our Evolutionary Classification of protein Domains (ECOD). Better computational tools are urgently needed to parse and classify domains from AlphaFold models automatically. Here we present a Domain Parser for AlphaFold Models (DPAM) that can automatically recognize globular domains from these models based on inter‐residue distances in 3D structures, predicted aligned errors, and ECOD domains found by sequence (HHsuite) and structural (Dali) similarity searches. Based on a benchmark of 18,759 AlphaFold models, we demonstrate that DPAM can recognize 98.8% of domains and assign correct boundaries for 87.5%, significantly outperforming structure‐based domain parsers and homology‐based domain assignment using ECOD domains found by HHsuite or Dali. Application of DPAM to the massive AlphaFold models will enable efficient classification of domains, providing evolutionary contexts and facilitating functional studies.