Toward a DNA Nanoprocessor: Optimization of Tile-Associated DNA Circuits

使用单个分子作为操作单元的纳米级处理器是使用半导体微处理器的现代计算机的一种有前途的替代方案。由分子构成的计算机可能比电子计算机更小，消耗的能量也更少。该项目的一个长期目标是从生物分子构建一种分子规模的处理器，称为DNA寡核苷酸。这种基于DNA的计算机的另一个优势是它们的生物兼容性，即能够以受控的方式与生物分子、细胞甚至器官相互作用。这一特性在生物体中控制和纠正代谢功能的分子装置的应用中，或者在诊断人类遗传和传染病的临床测试中，是至关重要的。最近，通过实施支持由DNA寡核苷酸制成的逻辑门之间的通信的原始设计，已经开发出由DNA寡核苷酸制成的可连接逻辑单元。在前人的研究中，设计了一组通信AND、NOT AND或逻辑门，并对其进行了表征。在结核分枝杆菌等病原菌的核酸序列分析中，这种逻辑门被证明比传统技术具有优势。通信门被连接到DNA瓷砖上，以产生简单的逻辑电路，这是现代计算机中使用的逻辑电路的对应物。该项目在DNA纳米处理器的开发中分为三个步骤。首先，DNA电路将由化学反应供电，为DNA计算机的持续运行提供能量。下一步是实现可重新设置和可重复使用的操作模式，使DNA计算机可以多次用于逻辑运算。这将通过使用生物催化剂来实现，例如消化DNA输入的酶和脱氧核酶，从而将分子装置重新设置为其原始状态。第三，将实现更大规模的DNA逻辑单元集成。更复杂的集成电路可以解决更复杂的计算任务。这将利用DNA纳米技术的最新发展--预先设计的结构中DNA链的可控自结合来实现。综上所述，该项目将解决在生产第一个DNA纳米处理器的过程中分子计算的三个重要问题。这将为未来的DNA纳米处理器奠定基础，DNA纳米处理器是未来智能医学分子纳米设备的关键组件。这项研究将通过将研究课题引入本科教学，对本科生和研究生进行研究培训，以及通过与佛罗里达州中部高中的合作开展推广计划，将研究与教育相结合。

A nano-scale processor that uses individual molecules as operational units is a promising alternative to the modern computers that use semiconductor microprocessors. A computer built from molecules is potentially smaller and consumes less energy than its electronic counterpart. A long-term goal of this project is to construct a molecular scale processor from biological molecules, called DNA oligonucleotides. An additional advantage of such DNA-based computers is their biocompatibility, which is the ability to interact with biological molecules, cells and even organs in a controlled fashion. This property is crucial in application of molecular devices in living organisms for the control and corrections of metabolic functions, or in clinical tests for diagnosis of human genetic and infectious diseases. Recently, connectable logic units made of DNA oligonucleotides have been developed by implementing an original design that supports communication between logic gates made of DNA oligonucleotides. In the prior studies, a set of communicating AND, NOT and OR logic gates was designed and characterized. It was demonstrated that such logic gates have advantages over conventional technologies in the analysis of nucleic acid sequences of pathogenic bacteria, such as Mycobacterium tuberculosis. The communicating gates were attached to the DNA tiles to produce simple logic circuits, a counterpart of logic circuit used in modern computers. This project makes next three steps in the development of a DNA nanoprocessor. First, DNA circuits will be powered by chemical reactions to provide energy for continuous operation of the DNA computer. Next step is to achieve re-settable and re-usable mode of operation, such that the DNA computer can be used multiple times for logic operations. This will be achieved by using biocatalysts, such as enzymes and deoxyribozymes which digest DNA inputs, thus resetting the molecular devise in its original state. Third, larger-scale integration of DNA logic units will be achieved. More complex integrated circuits can solve more complex computational tasks. This will be achieved using most recent developments in DNA nanotechnology - controllable self-association of DNA strands in predesigned structures. To sum up, this project will solve three important problems of molecular computation on the way to the production of a first DNA nanoprocessor. This will lay a foundation for the future DNA nanoprocessors, a key component of smart medical molecular nanodevices of the future. The research will be integrated with education through introducing research topics into undergraduate teaching, research training of students at undergraduate and graduate levels, and the outreach program through partnerships with Central Florida high schools.