Rational Design of DNA Sequences with Non-Orthogonal Binding Interactions

IF 4.7 2区 生物学 Q1 GENETICS & HEREDITY
Mobile DNA Pub Date : 2023-01-01 DOI:10.4230/LIPIcs.DNA.29.4
Joseph Don Berleant
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引用次数: 0

Abstract

Molecular computation involving promiscuous, or non-orthogonal, binding interactions between system components is found commonly in natural biological systems, as well as some proposed human-made molecular computers. Such systems are characterized by the fact that each computational unit, such as a domain within a DNA strand, may bind to several different partners with distinct, prescribed binding strengths. Unfortunately, implementing systems of molecular computation that incorporate non-orthogonal binding is difficult, because researchers lack a robust, general-purpose method for designing molecules with this type of behavior. In this work, we describe and demonstrate a process for the rational design of DNA sequences with prescribed non-orthogonal binding behavior. This process makes use of a model that represents large sets of non-orthogonal DNA sequences using fixed-length binary strings, and estimates the differential binding affinity between pairs of sequences through the Hamming distance between their corresponding binary strings. The real-world applicability of this model is supported by simulations and some experimental data. We then select two previously described systems of molecular computation involving non-orthogonal interactions, and apply our sequence design process to implement them using DNA strand displacement. Our simulated results on these two systems demonstrate both digital and analog computation. We hope that this work motivates the development and implementation of new computational paradigms based on non-orthogonal binding.
非正交结合相互作用DNA序列的合理设计
分子计算涉及混杂的,或非正交的,系统组件之间的结合相互作用,通常发现在自然生物系统中,以及一些拟议的人造分子计算机。这种系统的特点是,每个计算单元,例如DNA链中的一个结构域,可以以不同的规定结合强度与几个不同的伙伴结合。不幸的是,实现包含非正交结合的分子计算系统是困难的,因为研究人员缺乏一种强大的、通用的方法来设计具有这种行为的分子。在这项工作中,我们描述并展示了一个过程的合理设计的DNA序列与规定的非正交结合行为。该过程利用了一个模型,该模型使用固定长度的二进制字符串表示大组非正交DNA序列,并通过其对应二进制字符串之间的汉明距离估计序列对之间的差异结合亲和力。仿真和一些实验数据支持了该模型在现实世界中的适用性。然后,我们选择了两个先前描述的涉及非正交相互作用的分子计算系统,并应用我们的序列设计过程使用DNA链位移来实现它们。我们在这两个系统上的仿真结果显示了数字和模拟计算。我们希望这项工作能够激励基于非正交绑定的新计算范式的开发和实现。
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来源期刊
Mobile DNA
Mobile DNA GENETICS & HEREDITY-
CiteScore
8.20
自引率
6.10%
发文量
26
审稿时长
11 weeks
期刊介绍: Mobile DNA is an online, peer-reviewed, open access journal that publishes articles providing novel insights into DNA rearrangements in all organisms, ranging from transposition and other types of recombination mechanisms to patterns and processes of mobile element and host genome evolution. In addition, the journal will consider articles on the utility of mobile genetic elements in biotechnological methods and protocols.
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