DiffPepDock:高效的蛋白质接和粘合剂选通过SE(3) -等效扩散
Yuzhe Wang1, Fanhao Wang1, Laiyi Feng2
1Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Protein science : a publication of the Protein Society
|October 15, 2025
概括
DiffPepDock是一个新的蛋白质接工具,使用等价扩散模型准确地模拟相互作用. 这种高效的方法通过改善结预测和补充结构预测工具来帮助药物发现.
科学领域:
- 计算生物学是一种计算生物学.
- 结构生物学是结构生物学.
- 药物发现 药物发现
背景情况:
- 精确的蛋白质-相互作用建模对于理解生物过程和开发新疗法至关重要.
- 现有的计算方法往往在准确性,概括性,效率和整合先前绑定信息方面扎.
研究的目的:
- 为了介绍DiffPepDock,一个高效和准确的蛋白质对接工具.
- 通过利用SE(3) -等效扩散模型来增强蛋白质-相互作用建模.
- 为药物发现和治疗开发提供实用工具.
主要方法:
- 开发了DiffPepDock,该工具使用SE(3) -等效扩散模型进行蛋白质-对接.
- 在合成蛋白质碎片复合体上预训练模型,并在实验性蛋白质结构上微调模型.
- 嵌入了用户指定的绑定先验,如图案或参考连接体,以指导口袋选择并提高准确性.
主要成果:
- DiffPepDock的准确性与AlphaFold3等最先进的方法相美,推断时间显著减少.
- 案例研究表明,即使在面临 AlphaFold3 局限性的具有挑战性的场景中,也能够成功地重建原生结合结构.
- 在in silico选中取得了竞争性表现,用于识别预测的蛋白质标上的结剂.
结论:
- DiffPepDock为蛋白质-接提供了一个实用和可靠的解决方案.
- 该工具补充了现有的生物分子结构预测方法,并有助于治疗建模.
- 公共可用性和交互式演示有助于在研究中更广泛地采用和应用.
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