Tapping the computing power of biological molecules gives rise to tiny machines that can speak directly to living cells.
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Base Sequence↗
Biomedical subjects
Yaakov Benenson
Publications and source records attributed to Yaakov Benenson.
Stochastic computing with biomolecular automata.
Stochastic computing has a broad range of applications, yet electronic computers realize its basic step, stochastic choice between alternative computation paths, in a cumbersome way. Biomolecular computers use a different computational paradigm and hence afford novel designs. We constructed a stochastic molecular automaton in which stochastic choice is realized by means of competition between alternative biochemical pathways, and choice probabilities are programmed by the relative molar concentrations of the software molecules coding for the alternatives. Programmable and autonomous stochastic molecular automata have been shown to perform direct analysis of disease-related molecular indicators in vitro and may have the potential to provide in situ medical diagnosis and cure.
Calibration↗
An autonomous molecular computer for logical control of gene expression.
Early biomolecular computer research focused on laboratory-scale, human-operated computers for complex computational problems. Recently, simple molecular-scale autonomous programmable computers were demonstrated allowing both input and output information to be in molecular form. Such computers, using biological molecules as input data and biologically active molecules as outputs, could produce a system for 'logical' control of biological processes. Here we describe an autonomous biomolecular computer that, at least in vitro, logically analyses the levels of messenger RNA species, and in response produces a molecule capable of affecting levels of gene expression. The computer operates at a concentration of close to a trillion computers per microlitre and consists of three programmable modules: a computation module, that is, a stochastic molecular automaton; an input module, by which specific mRNA levels or point mutations regulate software molecule concentrations, and hence automaton transition probabilities; and an output module, capable of controlled release of a short single-stranded DNA molecule. This approach might be applied in vivo to biochemical sensing, genetic engineering and even medical diagnosis and treatment. As a proof of principle we programmed the computer to identify and analyse mRNA of disease-related genes associated with models of small-cell lung cancer and prostate cancer, and to produce a single-stranded DNA molecule modelled after an anticancer drug.
Antineoplastic Agents↗
DNA molecule provides a computing machine with both data and fuel.
The unique properties of DNA make it a fundamental building block in the fields of supramolecular chemistry, nanotechnology, nano-circuits, molecular switches, molecular devices, and molecular computing. In our recently introduced autonomous molecular automaton, DNA molecules serve as input, output, and software, and the hardware consists of DNA restriction and ligation enzymes using ATP as fuel. In addition to information, DNA stores energy, available on hybridization of complementary strands or hydrolysis of its phosphodiester backbone. Here we show that a single DNA molecule can provide both the input data and all of the necessary fuel for a molecular automaton. Each computational step of the automaton consists of a reversible software molecule input molecule hybridization followed by an irreversible software-directed cleavage of the input molecule, which drives the computation forward by increasing entropy and releasing heat. The cleavage uses a hitherto unknown capability of the restriction enzyme FokI, which serves as the hardware, to operate on a noncovalent software input hybrid. In the previous automaton, software input ligation consumed one software molecule and two ATP molecules per step. As ligation is not performed in this automaton, a fixed amount of software and hardware molecules can, in principle, process any input molecule of any length without external energy supply. Our experiments demonstrate 3 x 10(12) automata per microl performing 6.6 x 10(10) transitions per second per microl with transition fidelity of 99.9%, dissipating about 5 x 10(-9) W microl as heat at ambient temperature.
Adenosine Triphosphate↗