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Nucleic Acid Computing and Its Potential to Transform Silicon-Based Technology

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Nucleic Acid Computing and Its Potential to Transform Silicon-Based Technology DNA and RNA Nanotechnology 2015; 2: 13–22 Research Article Open Access Seth G. Abels and Emil F. Khisamutdinov* Nucleic Acid Computing and its Potential to Transform Silicon-Based Technology DOI 10.1515/rnan-2015-0003 occurring molecular computer is a living cell. Cells Received July 21, 2015; accepted September 11, 2015 continuously process an enormous amount of signals Abstract: Molecular computers have existed on our planet (inputs) generated by a broad range of environmental for more than 3.5 billion years. Molecular computing factors such as temperature, pH, pressure, nutrients, devices, composed of biological substances such as nucleic signaling chemicals, macromolecules, etc. [1-5]. Once the acids, are responsible for the logical processing of a variety signal is processed, the appropriate response (output) is of inputs, creating viable outputs that are key components effected. Examples of such a response can include gene of the cellular machinery of all living organisms. We have silencing, enzymatic activity, cell proliferation, migration, begun to adopt some of the structural and functional and apoptosis. In the field of synthetic biology, there is knowledge of the cellular apparatus in order to fabricate tremendous interest in the fabrication of artificial “smart” nucleic-acid-based molecular computers in vitro and in nano-devices that can autonomously perform functions vivo. Nucleic acid computing is directly dependent on similar to the physiological behavior of living cells. These advances in DNA and RNA nanotechnology. The field functions, which utilize macromolecules such as DNA, is still emerging and a number of challenges persist. RNA, and proteins, include the storage, retrieval, and Perhaps the most salient among these is how to translate processing of inputs. a variety of nucleic-acid-based logic gates, developed Molecular computers use inputs of materials and by numerous research laboratories, into the realm of energy to achieve a specific purpose by repeatedly silicon-based computing. This mini-review provides some cycling them through certain states. They differ from basic information on the advances in nucleic-acid-based conventional computers in fundamental ways. Most computing and its potential to serve as an alternative that molecular computers are nanoscale objects, thus are can revolutionize silicon-based technology. subject to manifestations of universal physical laws which differ greatly from the macroscopic world of our senses Keywords: Molecular computer, RNA nanotechnology, [6-8]. For example, molecular computers have a small DNA nanotechnology, Logic Gates, Biocomputing, Silicon mass-to-volume ratio and move in viscous media rather based computing than in a vacuum or air. As a result, they cannot store momentum or kinetic energy as usefully as macroscopic devices do. In addition, they cannot store thermal energy for a significant period of time due to their extremely small 1 Introduction size, and must operate isothermally. Conformational changes in the moving parts of Molecular computers are natural and/or artificial molecular machines, driven by thermal agitation, devices in which macromolecules, including proteins create, modify and disrupt binding and catalytic sites and nucleic acids, mediate necessary functions. These for substrates, and after the free-energy landscapes that functions usually include three basic operations: govern their motions. This characteristic gives molecular sensing inputs, processing the inputs, and generating computers a distinct advantage, although harnessing specific outputs. The best-known example of a naturally this capability of nanoscale soft matter is proving to be one of the most challenging aspects of molecular design. Molecular devices can, however, store elastic potential *Corresponding authors: Emil F. Khisamutdinov, Department of energy with spring-like conformational distortions of their Chemistry, Ball State University, 3401 N Tillotson Ave, Muncie, Indiana 47306, USA, E-mail: [email protected] macromolecular parts or substrates [8]. They consist of Seth G. Abels, Department of Chemistry, Ball State University, soft, conformationally-flexible matter that can function Muncie, IN 47304, USA © 2015 Seth G. Abels, Emil F. Khisamutdinov, licensee De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License. 14 S.G. Abels, E.F. Khisamutdinov as ratchet-and-pawl devices to bias molecular motions made of semiconductor materials like silicon are tasked of their substrates or flexible subsystems in desired with the primary role of amplifying and switching directions [6]. electrical power. The semiconductor has positively- In bionics, many engineering principles have been and negatively-charged areas. Electricity will not flow adopted from the study of biological machineries (6-8). between these areas unless the conducting channel is A few historical examples of bionics include fixed-wing open, as shown in Figure 1B. The channel opens when a aircraft, whose design was both inspired and informed by conductor, such as an insulated metal plate, is electrified. the study of birds in flight, and Velcro, which was based For electrons to flow though the conducting channel, on the hook-and-loop mechanism by which burs cling to there must be a source (input) and drain (output) made clothing and fur. As the bionic approach to engineering of metal. Even if the input is charged, it cannot flow to ventures more into the micro- and nanoscale, many fields, the output unless the gate (metal plate in the middle) from computer science to medicine to robotics, could be is also charged. When the gate is charged, it opens a transformed. For instance, consider ribosomal RNA. The conducting channel that allows the electrons to flow from study, incorporation, and even flat-out mimicry of the the negative to positive areas, or from the source to the features of this naturally-occurring molecular computer drain (Figure 1b, right panel). The most fascinating quality may help us clear hurdles and uncover answers (as well about this device is that there are no moving parts, in the as more questions) related to the design and behavior of mechanical sense. Electricity alone is used to perform nanocomputers. Current research in the fields of DNA [9-13] the computer’s functions, toggling between ON and OFF. and RNA [14-18] nanotechnologies, as well as in molecular This turns out to be ideal for the assembly of logic gates engineering [19-21], support the model of nucleic acid - digital circuits which alternatively permit or deny the molecules as promising candidates to fabricate molecular passage of an electrical signal. The signal can pass only if devices or bio-computers. DNA and RNA molecules certain LOGICAL conditions are satisfied. As exemplified possess the programmable folding properties necessary to in Figure 2 A, an OR gate can be constructed by connecting carry out various applications ranging from a drug carrier two transistors to different power supplies (inputs) and [22, 23] to nano-chips [24]. allowing a current (output) to flow from either or both of This mini-review focuses on the recent advances these supplies directly to a light bulb. The ON and OFF in nucleic acid computing. It is organized as follows: states, in the case of the switches, can be represented as an introduction to the simple operations carried out by “1” and “0,” respectively. If at least one of the switches computer microchips, including their limitations; a review is ON, the light bulb will be powered and in its ON (or of DNA and RNA computing as an alternative to silicon- “1”) state. An AND gate can be assembled using similar based computing technology; and a summary of, and an principles. For this, the output wire of the first transistor outlook for, nucleic-acid based computing. needs to be connected to the input wire of the second transistor, as shown in the Figure 2B . In this case, both switches need to be ON for the bulb to be lit. The basic, 2 Silicon-Based Technology and its binary language of modern computers lies in the realm of Limitations Boolean logic, which is a mathematical system featuring just two variables, “1” and “0”. The common logic gate In computing devices, the input information is functions (AND and OR, as touched upon, but also XOR, mathematically processed into a digital signal. For NAND, NOR, and XNOR) employed in Boolean algebra, as example, in the case of a binary code, the basic unit of well as the truth tables which define each function, are information is written as a series of “0’s” and “1’s,” summarized in Figure 3. Note that some gates, such as indicating the two states of the logic circuit. To gain better NAND, NOR, and XNOR, are in their ON state by default, insight into molecular computer operations, we need to unlike the AND, OR, and XOR gates. In fact, NAND, NOR, look at the core of a computer – its microprocessor. The and XNOR gates can be viewed as inverses of AND, OR, microprocessor consists of different modules, each one and XOR gates, respectively. performing different operations, including adding and The overall computer performance (e.g. system storing numbers. The modules are made of numerous availability, response time, latency, throughput etc.) transistors, which are widely used in electronics, from roughly depends on the numbers of transistors embedded calculators to spacecrafts. A transistor is an electrically within the microchip or integrated circuit (IC). The driven switch that permits or denies the passage of capabilities of digital electronic devices have increased in electrons, as demonstrated in Figure 1. In brief, transistors lock-step with Moore’s Law, which posits that the number Nucleic Acid Nanotechnology: Promising Path to Altering Silicon Technology 15 Figure 1. Representation of a transistor - the core of any compu- Figure 2. Exemplified view of (A) an OR logic gate and (B) an AND ting device. (A) Example of a microprocessor chip showing variety logic gate, both emloying transistors. or colored modules. Each module or area of the chip contains multiple transistors, as demonstrated on the right.
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