Functional nucleic acids as substrate for information processing

Information processing applications driven by self-assembly and conformation dynamics of nucleic acids are possible. These underlying paradigms (self-assembly and conformation dynamics) are essential for natural information processors as illustrated by proteins. A key advantage in utilising nucleic acids as information processors is the availability of computational tools to support the design process. This provides us with a platform to develop an integrated environment in which an orchestration of molecular building blocks can be realised. Strict arbitrary control over the design of these computational nucleic acids is not feasible. The microphysical behaviour of these molecular materials must be taken into consideration during the design phase. This thesis investigated, to what extent the construction of molecular building blocks for a particular purpose is possible with the support of a software environment. In this work we developed a computational protocol that functions on a multi-molecular level, which enable us to directly incorporate the dynamic characteristics of nucleic acids molecules. To allow the implementation of this computational protocol, we developed a designer that able to solve the nucleic acids inverse prediction problem, not only in the multi-stable states level, but also include the interactions among molecules that occur in each meta-stable state. The realisation of our computational protocol are evaluated by generating computational nucleic acids units that resembles synthetic RNA devices that have been successfully implemented in the laboratory. Furthermore, we demonstrated the feasibility of the protocol to design various types of computational units. The accuracy and diversity of the generated candidates are significantly better than the best candidates produced by conventional designers. With the computational protocol, the design of nucleic acid information processor using a network of interconnecting nucleic acids is now feasible

An analysis of simple computational strategies to facilitate the design of functional molecular information processors

BACKGROUND: Biological macromolecules (DNA, RNA and proteins) are capable of processing physical or chemical inputs to generate outputs that parallel conventional Boolean logical operators. However, the design of functional modules that will enable these macromolecules to operate as synthetic molecular computing devices is challenging. RESULTS: Using three simple heuristics, we designed RNA sensors that can mimic the function of a seven-segment display (SSD). Ten independent and orthogonal sensors representing the numerals 0 to 9 are designed and constructed. Each sensor has its own unique oligonucleotide binding site region that is activated uniquely by a specific input. Each operator was subjected to a stringent in silico filtering. Random sensors were selected and functionally validated via ribozyme self cleavage assays that were visualized via electrophoresis. CONCLUSIONS: By utilising simple permutation and randomisation in the sequence design phase, we have developed functional RNA sensors thus demonstrating that even the simplest of computational methods can greatly aid the design phase for constructing functional molecular devices. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12859-016-1297-x) contains supplementary material, which is available to authorized users

An Extended Dot-Bracket-Notation for Functional Nucleic Acids

Functional nucleic acids are an attractive substrate for molecular computing. A nucleic acid molecule is a linear chain of covalently bound building blocks assembled in arbitrary order from a set of typically four nucleotides. Certain pairs of nucleotides weakly attract each other through short-range electrostatic interaction and, accordingly, complementary sequences of nucleotides can bind to each other. The complementary stretches of nucleic acids that attract each other can be part of two different molecules or two parts of a single molecule. Binding within a single molecule leads to a folding of the linear chain. This so called secondary structure is of great importance for the function of nucleic acids. The present paper is concerned with the representation of this secondary structure. We propose an extension for the syntax of the standard dot-bracket notation to increase its convenience and expressive power for both its use to communicate nucleic acid secondary structures among humans and machines. The extensions reflect our own requirements for the representation of nucleic acids for molecular computation, but should be useful for functional nucleic acids in general

Design of interacting multi-stable nucleic acids for molecular information processing

Despite an exponential increase in computing power over the past decades, present information technology falls far short of expectations in areas such as cognitive systems and micro robotics. Organisms demonstrate that it is possible to implement information processing in a radically different way from what we have available in present technology, and that there are clear advantages from the perspective of power consumption, integration density, and real-time processing of ambiguous data. Accordingly, the question whether the current silicon substrate and associated computing paradigm is the most suitable approach to all types of computation has come to the fore. Macromolecular materials, so successfully employed by nature, possess uniquely promising properties as an alternate substrate for information processing. The two key features of macromolecules are their conformational dynamics and their self-assembly capabilities. The purposeful design of macromolecules capable of exploiting these features has proven to be a challenge, however, for some groups of molecules it is increasingly practicable. We here introduce an algorithm capable of designing groups self-assembling of nucleic acid molecules with multiple conformational states. Evaluation using natural and artificially designed nucleic acid molecules favours this algorithm significantly, as compared to the probabilistic approach. Furthermore, the thermodynamic properties of the generated candidates are within the same approximation as the customised trans-acting switching molecules reported in the laboratory