使用人工扩展的基对字母来改进DNA结构设计,包括循环和不匹配热力学参数
Tuan M Pham1, Terrel Miffin2, Hongying Sun3
1Department of Biochemistry & Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, NY.
bioRxiv : the preprint server for biology
|June 19, 2023
概括
将DNA基配对字母扩展到新的P-Z对,显著改善了DNA二次结构设计. 这一进步提高了预测准确度,减少了目标外折叠,加速了设计过程.
科学领域:
- 计算生物学 计算生物学
- 合成生物学 合成生物学
- 生物化学 生物化学
背景情况:
- 预测和设计DNA二次结构对于合成生物学应用至关重要.
- 目前的算法主要使用标准的AT和GC基配对规则.
- 扩大基配对字母为更准确和更强大的DNA设计提供了潜力.
研究的目的:
- 评估将新基对 (P-Z) 纳入DNA二次结构设计算法的影响.
- 确定新基对的热力学参数,并将其集成到现有的软件中.
- 通过使用扩展字母来评估设计准确性和效率的提高.
主要方法:
- 进行了47次光学化实验,以确定P-Z和G-Z波动对的热力学参数.
- 适应最近邻近的热力学参数,以扩展字母.
- 对P和Z核酸的外推循环,终端不匹配和悬挂的终端参数.
- 将新的参数集成到RNA结构软件包中.
- 在使用标准字母和扩展字母的Eterna游戏中的100个问题上测试了设计性能.
主要成果:
- 为P-Z和G-Z摇摆对开发了一套新的热力学参数,G-Z的稳定性与A-T对相当.
- 成功地将P和Z核酸纳入RNA结构,用于预测和设计.
- 使用扩展字母表解决了100个设计问题中的99个,超过了标准的仅使用DNA的设计.
- 降低了正常化组合缺陷 (NED) 值,表明目标结构较少,P-Z设计的平均NED为0.040,标准设计的NED为0.074.
- 通过包含P-Z对来解决设计问题,缩短了对接时间.
结论:
- 将DNA基配对字母扩展到A-T和G-C之外,包括P-Z对,显著提高了二次结构设计.
- 新的热力学参数和软件集成可以更准确地预测和设计DNA结构.
- 这项工作建立了将新型核酸纳入计算DNA设计工作流程的管道,为更复杂的合成生物学应用铺平了道路.
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