使用蛋白序列的深度生成模型设计重叠基因的设计
Gun Woo Byeon1, Marc Expòsit2,3,4, David Baker3,4,5
1Department of Electrical and Computer Engineering, University of Washington, Seattle, WA, USA.
bioRxiv : the preprint server for biology
|July 14, 2025
概括
叠加基因 (OLG) 在病毒中很常见. 这项研究表明,合成的OLG可以编码不同的蛋白质结构,这表明它们是可访问和有用的基因工程.
科学领域:
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
- 合成生物学 合成生物学
背景情况:
- 病毒经常利用重叠基因 (OLG) 在替代的读取框架中,尽管蛋白质序列空间减少了.
- 关于蛋白质折叠的氨基酸序列的退化以及重叠功能蛋白质的可行性仍然是开放的问题.
研究的目的:
- 为了研究氨基酸序列是否可以容纳功能蛋白质折叠在重叠的安排.
- 使用先进的生成模型设计合成OLG并评估其可行性.
主要方法:
- 设计了重叠的序列,针对两个不同的蛋白质家族.
- 采用最先进的生成模型进行序列工程.
- 在合成的OLG中编码了独特的,高度排序的de novo蛋白质结构.
主要成果:
- 在in silico和实验评估中取得了令人惊的高成功率.
- 证明遗传代码的约束不会显著阻碍在交替阅读框架中同时进行3D折叠.
- 证实了工程功能性的可行性,重叠的蛋白质结构.
结论:
- 叠加的基因序列在标准遗传密码下的折叠约束没有显著的限制.
- OLG 序列在自然界中可能经常可访问.
- 合成的OLG为压缩和约束遗传电路提供了一个有希望的策略.
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