停靠的地方

IF 12.9 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nature chemical biology Pub Date : 2024-07-29 DOI:10.1038/s41589-024-01695-1

Grant Miura

引用次数: 0

摘要

深度学习工具（如 AlphaFold2 (AF2)）的开发能够对蛋白质结构进行高置信度预测，为实验得出的结构提供了潜在的替代方案。AF2 还被设想用于帮助通过虚拟筛选确定新配体。然而，对 AF2 生成的结构与实验结构进行的回顾性对接分析表明，在预测配体结合位点方面结果不一。Lyu 等人以 σ2 受体和 5-HT2A 受体为候选受体进行了前瞻性分析，以测试 AF2 的性能。这些受体的 AF2 模型是在实验结构报告之前预测的。两个数据集显示出良好的一致性，可能消除了回顾性分析中可能出现的偏差。研究小组针对 AF2 生成的受体模型和实验结构，使用 4.9 亿到 16 亿分子的化学多样性库进行了大规模对接筛选。对于这两种受体，AF2和实验筛选活动的命中率、亲和力和Ki值都很相似，尽管筛选的化学结构并不相似。对5-HT2A的AF2特异性命中的冷冻电镜（cryo-EM）分析证实了预测的对接相互作用，表明AF2模型可用于鉴定新配体。此外，5-HT2A 筛选显示，与冷冻电镜结构相比，AF2 模型产生的化合物具有更高的效力和选择性。虽然这些发现对其他蛋白质的通用性尚不清楚，但 Lyu 等人的发现支持了利用 AF2 衍生结构进行对接以发现配体的潜在用途：Science 384, eadn6354 (2024)

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

A place to dock

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Nature chemical biology 生物-生化与分子生物学

CiteScore

23.90

自引率

1.40%

发文量

238

审稿时长

12 months

期刊介绍： Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.

期刊最新文献

Engineering a xylose fermenting yeast for lignocellulosic ethanol production A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion Evading resistance at the double Protein Degradation in Focus