Thermodynamic and first-principles biomolecular simulations applied to synthetic biology: promoter and aptamer designs,Molecular Systems Design & Engineering

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Thermodynamic and first-principles biomolecular simulations applied to synthetic biology: promoter and aptamer designs
Molecular Systems Design & Engineering ( IF 3.2 ) Pub Date : 2017-11-30 00:00:00 , DOI: 10.1039/c7me00083a
Kristin V. Presnell _{1,

2,

3,

4} , Hal S. Alper _{1,

2,

3,

4,

5}

Affiliation

A major challenge in the field of metabolic engineering and synthetic biology is the design of DNA elements, most often promoters, that achieve precisely targeted levels of expression of a given protein. The most widely applied strategy for addressing this challenge includes making libraries of thousands of mutants, then screening and selecting each mutant in the hopes of finding a favorable change to the DNA of interest which yields the desired expression level. Even with rational approaches to the design of these mutants, this process is slow and labor-intensive and requires improvements in high throughput screening methods to improve discovery rates. Biomolecular models (designed from a combination of first-principles thermodynamics and empirical data) and solution of these models through simulation, bypass these approaches, enabling nucleotide and amino acid level resolution by carrying out screening processes in silico or allowing for a more rational method of design. This review examines recent advances in biomolecular simulations and methods of subsequent data analysis in their role of designing functional DNA, RNA, and protein elements. We provide an orienting introduction to design choices in biomolecular simulations then discuss major recent developments in simulation technology with a more intensive focus on promoter and aptamer design. We then conclude with both a forward-looking prospectus on the field as well as pitfalls and areas for further study.

中文翻译：

用于合成生物学的热力学和第一性原理生物分子模拟：启动子和适体设计

代谢工程和合成生物学领域的主要挑战是DNA元件（最通常是启动子）的设计，这些元件可精确达到给定蛋白质表达的目标水平。解决这一挑战的最广泛应用的策略包括建立成千上万个突变体的文库，然后筛选和选择每个突变体，以期找到对目的DNA有利的变化，从而产生所需的表达水平。即使采用合理的方法设计这些突变体，该过程也是缓慢且费力的，并且需要改进高通量筛选方法以提高发现率。生物分子模型（由第一性原理热力学和经验数据共同设计）以及通过仿真对这些模型进行求解，从而绕开了这些方法，在计算机芯片上或允许设计的更合理的方法。这篇综述检查了生物分子模拟的最新进展以及后续数据分析方法在设计功能性DNA，RNA和蛋白质元素中的作用。我们为生物分子模拟中的设计选择提供了定向介绍，然后讨论了模拟技术的主要最新进展，重点是启动子和适体设计。然后，我们以该领域的前瞻性招股说明书以及陷阱和有待进一步研究的领域作总结。

更新日期：2017-11-30

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