一个全原子蛋白生成模型
Alexander E Chu1,2, Lucy Cheng3, Gina El Nesr1,2
1Biophysics Program, Stanford University.
bioRxiv : the preprint server for biology
|June 9, 2023
概括
我们开发了Protpardelle,这是一个用于蛋白质设计的全原子扩散模型. 这种模型可以生成具有精确化学特征的新型蛋白质结构和序列,从而推进蛋白质工程.
科学领域:
- 生物化学和结构生物学
- 计算生物学和生物信息学
- 在分子设计中的人工智能.
背景情况:
- 蛋白质通过化学相互作用发挥作用,主要是通过侧链,这需要精确的蛋白质设计建模.
- 现有的生成模型在管理蛋白质结构和序列的连续和离散性质方面面临挑战.
- 全原子建模对于捕捉蛋白质的详细化学行为至关重要.
研究的目的:
- 为蛋白质结构开发一个全原子生成模型.
- 为了使蛋白质结构和序列的同时设计.
- 为了产生具有精确化学性质的新型蛋白质.
主要方法:
- 开发了Protpardelle,这是蛋白质结构的全原子扩散模型.
- 实施了一个新的叠加方案来管理侧链状态.
- 集成模型与顺序设计方法进行共同设计.
主要成果:
- 生成的蛋白质表现出高质量,多样性和新性.
- 模拟的侧链准确地复制了天然蛋白质的化学特征和行为.
- 证明了全原子蛋白质结构和序列的成功联合设计.
结论:
- Protpardelle允许全原子蛋白质设计,包括功能性图案的脚手架.
- 该模型为蛋白质工程提供了一个没有骨干和旋转器的方法.
- 这项工作推进了de novo蛋白质设计和功能站点工程的生成建模.
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