pH-Controlled Detachable DNA Circuitry and Its Application in Resettable Self-Assembly of Spherical Nucleic Acids
https://pubs.acs.org/doi/abs/10.1021/acsnano.0c02329
Through Hogsteen interactions, DNA can form triple helices that are sensitive to PH variations. Triplexes form when pH is low, and break when pH is high. In this paper, the authors harness the formation of triplexes to build toeholds for strand displacement reactions. The kinetics of the displacement reactions are dependent of the formation of the triple helix, and they can even be stopped or resumed by changing the pH in the solution. Finally, they build a system with 2 triple helices that activate at different pH and can aggregate or disaggregate gold nanoparticles, just by changing the pH, without producing waste duplexes.
Preparation of a Millimeter-Sized Supergiant Liposome That Allows for Efficient, Eukaryotic Cell-Free Translation in the Interior by Spontaneous Emulsion Transfer
https://pubs.acs.org/doi/pdf/10.1021/acssynbio.0c00173
This paper describes an improved protocol to increase the efficiency of eukariotic cell-free translation. The conventional protocols are limited by high concentrations of sucrose that affect protein translation inside vesicles. They optimized the preparation conditions to permit supergiant unilamellar vesicle (SGUV) formation at a much lower concentration of sucrose that has almost no effect on translation. Under the optimized conditions, they observed a high rate of succesful SGUV formation (>90%) and a decent stability of the formed SGUVs (>60 min). These SGUVs are expected to serve as research tools in cell-free synthetic biology and as foundations for artificial cell-based biosensors.
Rational design of aptamer switches with programmable pH response
https://www.nature.com/articles/s41467-020-16808-2
Non-conventional base-pairs (Hoogsteen, Wobble) can introduce additional degree of tuneability to standard Watson- Crick base-pairs. A change in the environmental pH, which changes the propensity of such base-pairs, can be utilised to fine tune DNA-based systems. In this paper, the authors describe a designed strand where a linker domain forms a DNA triple helix at lower pH, and therefore destabilises a duplex of an ATP aptamer and a displacement domain, and thereby allows the aptamer to bind ATP with a 1000 fold higher binding efficiency compared to an elevated pH. In a separate approach, they demonstrated another design where the aptamer binds ATP better at higher pH. By combining these two feature in orthogonal fashion, the authors demonstrate that it is indeed possible to design an aptamer which binds its target in a very narrow pH range. Furthermore, since the actual structure of the aptamer sequence is not altered during the pH change, and the added domains show the pH responsiveness, the authors argue that this strategy can turn any aptamer into a pH switch with the need minimal alterations of the sequences.
DNA Logic Circuits Based on Accurate Step Function Gate
https://ieeexplore.ieee.org/abstract/document/9121273
A step function gate is achieved by combining step activation and a threshold module. This module was used to construct AND, OR, and XOR gates. The result was simulated using DSD.
Aminoacyl-tRNA Synthetases
https://rnajournal.cshlp.org/content/early/2020/04/17/rna.071720.119.abstract
This is a comprehensive review of Aminoacyl-tRNA synthetases (aaRS), the family of enzymes responsible for charging transfer-RNAs (tRNA) with their cognate amino acid (AA). There is a unique aminoacyl-tRNA synthetase for each of the 20 amino acids. The accuracy of protein synthesis relies on both the matching of mRNA:tRNA duplexes in the ribosome, and the accuracy of amino acid:tRNA charging in aaRSs. AaRSs function as templates for the specific dimerisation of the two types of genetic molecule, amino acids and nucleic acids. Therefore these are the only enzymes that really do the job of converting the genetic code from nucleic acids to amino acids.
Charged tRNAs are synthesised in two phases (AA binding and attack, followed by tRNA binding, hybridisation, and release) coupled to the turnover of one molecule of ATP to AMP. Some aaRSs exhibit post-charging editing, indicating that kinetic proofreading may be used to increase specificity beyond the equilibrium limit.
Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet
https://www.nature.com/articles/s41467-019-11402-7
The present paper details how, in molecular systems, due to the local lack of detailed balance between the fluxes in macromolecular machines, it is possible to describe the working of out-of-equilibrium systems via two different mechanisms: (a) energy ratchets (in which the driving force of the system is a change in the external conditions -such as redox potential light or pH- that drives the system to a new equilibrium) and (b) information ratchets (in which a catalyst biases the system by controlling and favouring the energy barriers we want). The paper, besides making the distinction, and showing the criteria to clasify molecular machines, shows different examples of each coming from different parts of chemistry explaining what properties of the system arise from underlying kinetic asymmetries.
Programming and simulating chemical reaction networks on a surface
https://doi.org/10.1098/rsif.2019.0790
Clamons, Qian and Winfree present an exploration of a previously-introduced surface CRN model of molecular computing. They present an authoritative review of the topic, and then demonstrate how to deal with some of the challenges of implementing complex surface-based CRNs, in particular issues with asynchronicity. The authors then show how these strategies can be used to build an extremely broad range of interesting molecular circuits. I have no concerns about the accuracy of the results.
The examples and supporting code are extremely effective pedagogically and the paper is fun to read - it should inspire theorists and experimentalists alike.
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