Biomolecular computing systems principles, progress and pote(4)

2019-03-22 14:26

specific ways of encoding the symbols, the states and state transitions. A crucial challenge that is evident in those designs is symbol writing: modifying a small portion of the tape in a particular location (somewhat like RNA editing) at each computation step. Thus, these ideas are still awaiting experimental implementation.

第二大类模型,包含状态机,处理存储在磁带上的离散数据单元-符号(图3)。根据特定的规则处理这些符号。虽然这些模型通常被用来证明语句的可计算性,通过转录和翻译,使他们对于实际的生物分子计算来说,可以成为合理的设计。至今已经成功的试验验证了简单的只读模式,如有限自动机。理论上的分子图灵机的设计建议采用独特的方式对符号、状态和状态转换进行编码。在这些设计中一个显而易见的关键性挑战是符号的书写:每个计算步骤在一个特定的位置修改磁带的一小部分(有点像RNA修订)。因此,这些想法仍在等待实验验证。

图 3

In a finite automaton, the tape symbols can be replaced with a temporal sequence of short events, resulting in ‘reactive’ cell control systems that wait for their inputs while preserving the memory of the past. A molecular implementation was proposed in which the environmental trigger activates a recombinase that in turn modifies a specific DNA sequence (such as a gene promoter). This modified DNA is identified with a new system state because it remains stable and because it determines which DNA modification (that is, the next ‘state’) is caused by the next trigger (that is, the next ‘symbol’).

在一个有限自动机中,磁带符号可以用短事件的瞬时序列代替,导致被动的单元

控制系统,在等待输入的同时保留了过去的记忆。提出了一个分子实现,环境触发激活重组酶,修饰特定的DNA序列(如基因启动子)。这种修饰的DNA被确定为一个新的系统状态,因为它是稳定的,并且决定了哪个DNA修饰(即下一个“状态”)是由下一个触发引起的(即下一个“符号”)。

Other models 其他模型

A number of new models of computations explicitly consider the biological or chemical medium as well as specific biochemical transformations. Among them are: splicing systems, which use recombinant DNA protocols to generate new sequence libraries in a programmable fashion; membrane computing, which is a model that requires compartmentalization and information exchange between compartments; computation in excitable media, which builds on processes such as oscillating Belousov–Zhabotinsky reactions and may have relevance to pattern establishment in embryogenesis; and computation based on gene recombination, which was inspired by the elaborate gene rearrange-ment in ciliates.

一些新的计算模型明确地考虑到生物或化学介质以及特定的生化变化。其中包括:剪接系统,即利用DNA重组协议以一种可编程的方式产生新的序列库;膜计算,一个隔室之间需要分割和信息交换的模型;激发介质计算,建立在Belousov–Zhabotinsky振荡反应等过程上,可能和胚胎发育的模式构建相关;基于基因重组的计算,灵感来自于纤毛虫上的复杂的基因重排。

The notions of distributed computing and amorphous computing are also instrumental for conceptualizing large stochastic networks of chemical processes and information processing by multiple interacting agents (for example, bacterial cells or organelles), respectively. These works are another

important source of inspiration for future experimental molecular computing. 分布式计算和无定形计算的概念对化学过程的大规模随机网络和多个相互作用的中介的信息处理是有帮助的,(例如,细菌细胞或细胞器)。这些工作是未来分子计算实验的一个重要的灵感来源。

Experimental logic circuits 逻辑电路的实验

Abstract logic networks are easy to sketch but are difficult to implement with molecules. Any logic circuit blueprint requires a set of real-world switches that comprise the basic gates and their networks. In computer engineering, transistors are universally used to implement switching schemes of almost unlimited complexity. Such truly universal building blocks may never become available for molecular systems because, unlike the circuit board, where all of the gates are physically localized and separated, molecular components diffuse and mix.

抽象的逻辑网络易于表示,但用分子实现就很难了。任何逻辑电路的设计需要一套现实世界的开关,由基本的门和网络结构构成。在计算机工程,普遍采用晶体管来解决无限复杂的开关切换方案。这种现实意义上的通用的构建模块可能永远不会成为可用的分子系统,不像电路板,基本所有的门都是物理上局部定位和分开的,而分子总是扩散和混合的。

Thus, barring compartmentalization of each component in its own membrane, gates and wires must be structurally distinct. Features required from an effective molecular switch or gate include: the existence of a robust digital regime (that is, input levels that produce either a very low or a very high (saturated) output); gate scalability, which is the capacity to receive an

increasing number of inputs without dramatic design alterations; and com-posability, which is the capacity to operate together with other gates in parallel and/or in cascades in a predictable manner. In theory, some biological building blocks possess all of these features. In practice, increasing the size of biochemical and biological circuits is challenging even when it is theoretically possible.

因此,除非每个组件都划分在自己的隔膜内,门和线必须在结构上有所区分。一个有效的分子开关或门所需的特点包括:一个强大的数字制度(即输入必须产生一个非常低或非常高(饱和)的输出);门的可扩展性,可以在不进行较大的改动下,接收更多的输入;组合性,能够以一种可预见的方式并行的和其他的门进行与或运算的级联。在理论上,一些生物模块都拥有这些功能。尽管在理论是是可行的,但是在实践中,生物分子电路的规模增大是一项较大的挑战。 In biochemical circuits, interacting sets of single- and double-stranded DNA oligonucleotides seem to provide the answer because interactions between DNA strands follow Watson–Crick rules and thus can be predicted computationally with a high certainty. In cells, these DNA structures are unstable and the development of additional non-native, ‘orthogonal’ cellular processes is still in its infancy.

在生化电路中,相互作用的单、双链DNA寡核苷酸组 似乎提供了可行的方案,由于DNA链之间的沃森–克里克作用,可以预见到一个高精确度的计算。在细胞中,由于这些DNA结构是不稳定的,以及附加的非天然结构,正交的细胞过程仍处于起步阶段。

Thus, native building blocks are used as the basis for novel switches to ensure their operation in cells. Below we describe switch and circuit design based on DNA, followed by RNA and then protein building blocks. composed of multiple


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