Jinzou Ningen – Artificial Human project

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Exploring possibilities

Protein Synthesis; Design Of Synthesis Unit

In the previous article on protein synthesis [1] we addressed the way biological (eukaryotic) cells synthesize the proteins which make up said cells and other structures in the body in addition to performing various other tasks. The basic summary of this process is transcription of DNA into messenger RNA (mRNA) which is then fitted into ribosomes which use transfer RNA (tRNA) as an intermediate form to translate codons of three nucleotides on the mRNA into one of about twenty possible alpha-amino acids [2]. The resulting string of amino acids then folds due to molecular forces into a 3D form, its final shape determining its function due to the active surfaces on the outside of the protein.

In artificial synthesis of proteins there are a few possible ways to approach this issue, which will be the focus of this article. The most basic approach is essentially the use of an artificial ribosome, whereby the transfer of mRNA through it is simulated and tRNA units with alpha-amino acids are present. The faster, superior, but possibly more complex approach is to directly attach the relevant amino-acid onto the protein string. We’ll examine both option.

The artificial ribosome option (AR approach) is attractive in that it stays close to the existing eukaryote setup, something which we’re all familiar with. We can use existing tRNA, and just keep adding the proper amino-acids to the fluid. The artificial ribosome would need to receive information and adapt the template on its surface based on it to protrude the relevant codons for the anti-codon of the matching tRNA unit to attach to and thus proceed with the formation of the protein string. This means a fairly light-weight setup, within reach of existing nano-technology. The synthesis of an AR unit would be quite involved, but not impossible. The communication protocol would be interesting, and may result in something very much akin to mRNA. In the end this may end up being a fairly complex imitation of the biological system.

On the other hand there’s the ‘2D printer’ setup of the Direct Attachment (DA) approach, which at first does seem more complex, but reduces protein synthesis to the very basics. There’s no more mRNA, ribosome, tRNA and free-floating resources and data in fluid. Instead there’s a single unit which has reservoirs containing the alpha-amino acids which could be drawn into the reservoirs or otherwise refilled, which opens or closes the relevant reservoirs when a particular amino acid is needed. Either the protein string could be moved along the reservoirs, or the reservoirs could be moving in a kind of head, or a pick-and-place approach could be used to transport the amino acid. Or maybe a simple transport system, such as the endoplasmic reticulum uses.

Frankly, given the choice I would go with the DA approach for the simple reason that it allows for many adaptations and much more control. The communication protocol is still an issue, but by dropping the complex addressing of mRNA to tRNA to protein string and using a simple direct addressing in theory this shouldn’t be too much of an issue. As remote control may be desirable the use of something reliable such as the electric signaling of a nerve cell could be used. One wouldn’t be limited to purely biological structures either, and use semi-conductor techniques, akin to those of lab-on-a-chip configurations.

The next article on protein synthesis should further work out the design of the DA approach. Please look forward to it đŸ™‚

Maya

[1] https://jinzouningen.wordpress.com/2012/03/02/protein-synthesis-polymer-design/
[2] http://en.wikipedia.org/wiki/Amino_acid

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Filed under: Polymers, Synthesis, , , , , , ,

Protein Synthesis; Polymer Design

To the average person ‘polymer’ brings to mind images of rubbers and plastics. They are indeed polymers [1], but only a small number of examples. One of the most intricate collections of polymers has to be biological life forms like you, me, animals in general as well as plants and single-celled biological systems. Proteins form most of the solid mass of a human body and every single one of them is a protein.

The way a single cell functions is that it stores the information needed to form protein polymers in the form of deoxyribonucleic acid  (DNA). DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. Attached to each sugar is one of four types of molecules called nucleobases, cytosine, guanine, adenine and thymine (C, G, A, T respectively).

During transcription of active (uncovered) genes in the DNA these nucleobases are transcribed into strings of ribonucleic acid (RNA), whereby the thymine is exchanged for uracil (U). These RNA strings are referred to as messenger RNA (mRNA). These mRNA strings are used as the template by the polymer synthesis engines of the cell: the ribosomes [2]. This process is known as translation.

Each three nucleobases in mRNA, called a codon, encode one type of amino acid, or monomer. The thus encoded monomers will be assembled in the specified order by the ribosome. It first latches on to the mRNA string, then runs across it whereby it uses transfer RNA (tRNA) which has a complimentary anti-codon on one end and the matching amino acid on the other end to assemble the resulting polymer string.

After translation the polymer string usually undergoes structural changes (folding) as well as some chemical modifications. This results in the final, functional protein.

It’s quite a nice example of how to construct a storage and translation/synthesis unit out of only polymers. It also contains the basics of where medical science is taking us. More and more often we end up fixing issues in medicine on a protein level, whether it concerns cancer, Alzheimer’s or similar diseases whereby something went wrong during the above process.

Protein synthesis and design of custom proteins also forms the basis of two exciting new developments, namely in improving an existing body and in creating a cell and ultimately a body from scratch. Additionally there is the possibility of tapping into this system and modifying it to link it up with, say, a computer.

Imagine if the polymer structure wasn’t stored in DNA, but in a computer, and didn’t use mRNA, ribosomes and the like for translation into proteins. What if a different unit than a ribosome was used to assemble the amino acids, for example by presenting the proper receptor at the right time to coax the two amino acids to be matched together? It could thus simulate the functioning of the tRNA molecules while presenting a direct link between the digital design and the resulting string of amino acids. It could be used universally for any type of monomer, really.

Designing a protein is hard because its functioning is based on its 3-dimensional structure and functional units presented to external receptors and molecules. The polymer design language I’m working on at this point has to find the proper links and simulation accuracy to allow one to describe a functional 3D polymer which can then be unfolded into a 2D string and sent to the aforementioned translation unit.

I hope to present more details on this Polymer Design Language (PDL) and the associated synthesis tools soon, including hopefully some examples and simulation results in GROMACS [3] or similar. Until then.

Maya

[1] http://en.wikipedia.org/wiki/Polymer
[2] http://en.wikipedia.org/wiki/Ribosome
[3] http://www.gromacs.org/

Filed under: Polymers, Synthesis, , , , , ,

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Maya Posch: professional software engineer and game developer. Graphics artist and all-around science junky.

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