Biomolecular computers with multiple restriction enzymes

Abstract

The development of conventional, silicon-based computers has several limitations, including some related to the Heisenberg uncertainty principle and the von Neumann “bottleneck”. Biomolecular computers based on DNA and proteins are largely free of these disadvantages and, along with quantum computers, are reasonable alternatives to their conventional counterparts in some applications. The idea of a DNA computer proposed by Ehud Shapiro’s group at the Weizmann Institute of Science was developed using one restriction enzyme as hardware and DNA fragments (the transition molecules) as software and input/output signals. This computer represented a two-state two-symbol finite automaton that was subsequently extended by using two restriction enzymes. In this paper, we propose the idea of a multistate biomolecular computer with multiple commercially available restriction enzymes as hardware. Additionally, an algorithmic method for the construction of transition molecules in the DNA computer based on the use of multiple restriction enzymes is presented. We use this method to construct multistate, biomolecular, nondeterministic finite automata with four commercially available restriction enzymes as hardware. We also describe an experimental applicaton of this theoretical model to a biomolecular finite automaton made of four endonucleases.

DNA Computing: Concepts for Medical Applications

“…It is also acceptable to use multiple type IIB restriction endonucleases that act alternately in a single reaction mixture as well as to use restriction enzymes of other classes, for instance Class II, which cut the DNA chain only in one direction from the restriction site. This is of interest particularly in the aspect of earlier laboratory studies on the applicability of multiple restriction enzymes [5,6], as well as the concept of a theoretical design of a push-down automaton with the use of multiple restriction enzymes [32]. It is worth mentioning that, in the area of DNA computing, earlier practical solutions based on the use of restriction enzymes, only offered the possibility of reading the information encoded in the DNA, but not that of writing it [3,5].…”

“…This effect of the type IIB restriction endonucleases enables the biomolecular computer to be programmed so that, after cutting the DNA chain, the enzyme writes information on the read-out DNA fragment (Figure 6B)-this is similar to the case of the biomolecular push-down automaton [8]. It is worth mentioning that a representative of the type IIB restriction endonucleases, BaeI, was used in practical experiments aimed at the implementation of the biomolecular computer involving multiple restriction enzymes [6]. This provided an experimental ground in the area of DNA computing for constructing various practical solutions based on type IIB restriction endonucleases.…”

“…Further studies, including experimental ones, were carried out by our and Ehud Shapiro's teams, and demonstrated the potential of restriction enzymes in developing practical programmable biomolecular nanodevices, functioning in actual laboratory conditions [3][4][5][6]. In 2001, Ehud Shapiro's group built biomolecular computers in which double-stranded DNA was employed for encoding processed input data (symbols encoded in the input word).…”

“…The use of restriction enzymes in typical laboratory conditions requires optimization of reaction conditions [5] and an appropriate approach to encoding various components of biomolecular computers, especially when multiple restriction enzymes are used. A number of laboratory experiments were carried out using multiple restriction enzymes, operating alternately on DNA chains in a single reaction mixture [5,6]. After solving various practical problems, we developed an algorithmic method that enabled an ad hoc addition of more restriction enzymes acting alternately on the appropriately encoded DNA [6].…”

“…A number of laboratory experiments were carried out using multiple restriction enzymes, operating alternately on DNA chains in a single reaction mixture [5,6]. After solving various practical problems, we developed an algorithmic method that enabled an ad hoc addition of more restriction enzymes acting alternately on the appropriately encoded DNA [6]. Understanding the successive properties of the biomolecular computers led us to the formulation of a new mathematical theory involving a base formal apparatus concerning performance of computation by means of a single restriction enzyme and a double-stranded DNA [7].…”