Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs.

Rational design of DNA sequences for nanotechnology, microarrays and molecular computers using Eulerian graphs.
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使用欧拉图合理设计纳米技术、微阵列和分子计算机的 DNA 序列。

DOI:
10.1093/nar/gkh802
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发表时间:
2004
影响因子:
14.9
通讯作者:
Moll,UteM
Moll,UteM
中科院分区:
生物学2区
文献类型:
--
作者:
Pancoska,Petr;Moravek,Zdenek;Moll,UteM

文献摘要

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核酸是现有和新兴纳米技术的首选分子。这些技术受益于易于制造的“DNA 处理元件”的大功能密度。为了实现所需的功能,目前设计多核苷酸序列的过程涉及根据一系列要求和参数对潜在候选物进行繁琐且费力的过滤。在这里,我们提出了一种用于快速合理设计大量 DNA 序列的全新方法。这种方法允许直接实现对生成序列的非常复杂和详细的要求,从而避免“强力”过滤。同时,这些序列的解链温度分布很窄。设计过程的分子部分可以在没有计算机辅助的情况下完成,使用有效的“人体工程”方法,通过绘制代表所有生成序列的单个蓝图来完成。此外,该方法消除了大量热力学计算的必要性。熔化温度只能计算一次(或根本不计算)。此外,序列的等稳定性与一组特定热力学参数的选择无关。介绍了微阵列 DNA 序列设计、通用微阵列 zip 序列和电子转移实验的应用。
Nucleic acids are molecules of choice for both established and emerging nanoscale technologies. These technologies benefit from large functional densities of ‘DNA processing elements’ that can be readily manufactured. To achieve the desired functionality, polynucleotide sequences are currently designed by a process that involves tedious and laborious filtering of potential candidates against a series of requirements and parameters. Here, we present a complete novel methodology for the rapid rational design of large sets of DNA sequences. This method allows for the direct implementation of very complex and detailed requirements for the generated sequences, thus avoiding ‘brute force’ filtering. At the same time, these sequences have narrow distributions of melting temperatures. The molecular part of the design process can be done without computer assistance, using an efficient ‘human engineering’ approach by drawing a single blueprint graph that represents all generated sequences. Moreover, the method eliminates the necessity for extensive thermodynamic calculations. Melting temperature can be calculated only once (or not at all). In addition, the isostability of the sequences is independent of the selection of a particular set of thermodynamic parameters. Applications are presented for DNA sequence designs for microarrays, universal microarray zip sequences and electron transfer experiments.