多模式扩散用于蛋白质序列和结构的联合设计
Shaowen Zhu1, Siddhant Gulati2, Yuxuan Liu1
1Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, USA.
Protein science : a publication of the Protein Society
|November 14, 2025
概括
本研究提出了一种新的计算方法,用于设计蛋白质序列和结构,从而实现更快,更具功能性的蛋白质生成. 实验结果显示了有希望的功能蛋白质设计,加速了未来的应用.
科学领域:
- 蛋白质工程是指蛋白质工程.
- 计算生物学 计算生物学
- 结构生物学 结构生物学
背景情况:
- 通过计算来设计功能性蛋白质对于基础科学和实际应用都至关重要.
- 现有的方法经常在单独的阶段设计蛋白质序列和结构,这可能是低效的.
研究的目的:
- 开发一个统一的生成框架,同时共同设计蛋白质序列和结构.
- 为了实现连贯和功能性蛋白质设计的跨模式相互作用.
主要方法:
- 一个生成框架,模拟蛋白质序列和结构的联合分布.
- 使用三种模式表示残留物:类型,位置和方向,每一种都是通过扩散过程建模的.
- 一个统一的架构,ReverseNet,带有图形注意力编码器和单独的投影仪,用于多式联网集成.
主要成果:
- 拟议的模型 (JointDiff和JointDiff-x) 对单体结构的可比性或更好的可设计性比双阶段模型更好.
- 模型速度快1-2个数量级,支持快速代设计.
- 对绿色光蛋白 (GFP) 设计的实验验证实产生了具有可测量的光的新型功能变体.
结论:
- 联合序列结构生成是可行的,可以加速功能性蛋白质设计.
- 该框架为计算蛋白质工程的未来进步提供了基础.
- 开源代码和模型可用于进一步的研究和应用.
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