Difference between revisions of "Molecular biology"
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Since this wiki is about APM we'll assume one is aiming for the latter (a non-medical structural application potentially useful for bootstrapping advanced APM). | Since this wiki is about APM we'll assume one is aiming for the latter (a non-medical structural application potentially useful for bootstrapping advanced APM). | ||
In that case the process works roughly like follows: | In that case the process works roughly like follows: | ||
| − | + | ---- | |
* "Backward engineering:" Determine the required sequence of amino acids such that the amino acid chain curls up into the desired shape (however this shape is determined {{wikitodo|check specific papers}}). <br>(Related: "inverse folding problem" and "de-novo protein engineering") | * "Backward engineering:" Determine the required sequence of amino acids such that the amino acid chain curls up into the desired shape (however this shape is determined {{wikitodo|check specific papers}}). <br>(Related: "inverse folding problem" and "de-novo protein engineering") | ||
* Digital encoding: Encoding the amino acid sequence into DNA base-pairs. (A simple straightforward trivial step.) | * Digital encoding: Encoding the amino acid sequence into DNA base-pairs. (A simple straightforward trivial step.) | ||
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* Inserting: (This is the genetic engineering step.) Introduce the synthesized DNA into a host organism. There are several methods. One needs a "vector" to carry the (here fully man made) DNA past the organisms cells defense mechanisms. As organisms often some bacteria are chosen since they breed fast. (There are loads of details in this step e.g. knowledge about the various ways life and virii reproduce.) | * Inserting: (This is the genetic engineering step.) Introduce the synthesized DNA into a host organism. There are several methods. One needs a "vector" to carry the (here fully man made) DNA past the organisms cells defense mechanisms. As organisms often some bacteria are chosen since they breed fast. (There are loads of details in this step e.g. knowledge about the various ways life and virii reproduce.) | ||
---- | ---- | ||
| − | * Breeding: Put the organisms in a nutrient solution and choose an optimal temperature. Naturally there are loads of things happening in the cells while growing and reproducing. Here is just the part that is most relevant for us. The part we are interested in most:<br>Transcription: translation of the protein encoding section of DNA (aka a gene) to | + | * Breeding: Put the organisms in a nutrient solution and choose an optimal temperature. Naturally there are loads of things happening in the cells while growing and reproducing. Here is just the part that is most relevant for us. The part we are interested in most:<br>Transcription: translation of the protein encoding section of DNA (aka a gene) to messenger-RNA (mRNA). DNA is like the high security mass data storage of the cell while mRNA is like a short disposable working copy. <br>Translation: Assembly of A protein based on the information encoded in the messenger-RNA (mRNA) <br>Self-folding: Right after (or actually during) the synthesis of the protein it curls up and self folds to a shape. |
---- | ---- | ||
* Extracting: Finally extract the desired protein out of the cells that made it and get them as pure as possible. | * Extracting: Finally extract the desired protein out of the cells that made it and get them as pure as possible. | ||
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---- | ---- | ||
* Analytics: Use various kind of (usually non optical) microscopes to check whether you actually made what you've intended to make. | * Analytics: Use various kind of (usually non optical) microscopes to check whether you actually made what you've intended to make. | ||
| − | + | ---- | |
Note that beside the core manufacturing of our desired protein there is also a much much longer string of other things going on. All the manufacturing for the reproduction of the organism and all the other subsystems of the organisms: energy, information, waste, ...) | Note that beside the core manufacturing of our desired protein there is also a much much longer string of other things going on. All the manufacturing for the reproduction of the organism and all the other subsystems of the organisms: energy, information, waste, ...) | ||
So this is quite a process and the throughput of this isn't very high. | So this is quite a process and the throughput of this isn't very high. | ||
Thus synthetic proteins currently (2017) are massively more expensive than raw biological products like e.g. food. | Thus synthetic proteins currently (2017) are massively more expensive than raw biological products like e.g. food. | ||
| + | |||
| + | Far term outlook: A main goal of APM is (beside a switch to more stiff materials than bio-foldamers) to switch that around and make advanced [[gem-gum]] products at least as cheap as food (on a per mass basis). | ||
== Notes == | == Notes == | ||
Proteins (and foldamers in general) tend to have have weak bonds between folds thus they may only feature [[topological atomic precision]] especially on their outside. Some tightly packed proteins might feature [[positional atomic precision]] inside (e.g. ion channel proteins) {{todo|investigate this}}. | Proteins (and foldamers in general) tend to have have weak bonds between folds thus they may only feature [[topological atomic precision]] especially on their outside. Some tightly packed proteins might feature [[positional atomic precision]] inside (e.g. ion channel proteins) {{todo|investigate this}}. | ||
| + | |||
| + | == Related == | ||
| + | |||
| + | * [[Foldamer R&D]] | ||
| + | * [[Synthetic biology]] | ||
| + | |||
| + | == External links == | ||
| + | |||
| + | === Wikipedia === | ||
| + | |||
| + | * [https://en.wikipedia.org/wiki/Molecular_biology Molecular_biology] | ||
| + | ---- | ||
| + | * [https://en.wikipedia.org/wiki/Protein_biosynthesis Protein_biosynthesis] | ||
| + | * [https://en.wikipedia.org/wiki/Protein_production Protein_production (biotechnological)] | ||
| + | * [https://en.wikipedia.org/wiki/Cell-free_protein_synthesis Cell-free_protein_synthesis] | ||
| + | * [https://en.wikipedia.org/wiki/Peptide_synthesis Peptide_synthesis] | ||
| + | ---- | ||
| + | * [https://en.wikipedia.org/wiki/Protein_purification Protein_purification] | ||
Latest revision as of 16:14, 30 May 2021
Molecular biology is about how life works in detail at the molecular scale. For an in depth definition of molecular biology please consult the wikipedia page about the topic and/or some other sources.
This article is not about molecular biology in general (there is plentiful excellent introductory material out there already). It is about molecular biology specifically in the context of advanced atomically precise manufacturing (APM).
Contents
Utilizing life's machinery
Why do so?
Making atomically precise structures is still pretty difficult with current technology (state 2017).
Shoving atoms around with needle tips has a lot of problems. See main articles "direct path" and "scanning probe microscopy" for details.
Using chemistry for making atomically precise structures suffers from specificity and scaling problems. It has the issue that the opening of new synthesis routes in many regards are more of a black art than a systematic engineering methodology. There are some interesting attempts to make some specific areas in the space of molecular structures more accessibly to systematic engineering though. (wiki-TODO: discuss this in more detail elsewhere on this wiki)
Utilizing life's machinery for making atomically precise structures has the advantage that it is already there and working. It poses a very useful option for starting the bootstrapping process towards advanced APM (gem-gum-tec). (See main article "incremental path".) Thus especially for early APM molecular biology might be highly relevant.
Why not?
While molecular biology is a very useful boosting tool at the early stages it is very different to the target technology. So at some point utilizing life's nanomachinery must be shed. (Later even foldamer technology in favor to crystolecules.)
To get common trapdoors out of the way:
- Using life's nanomachinery dose not always mean aiming at recreating something like life's nanomachinery.
(That would be synthetic biology not APM) - Using soft nanomachinery does not always mean aiming at soft nanomachinery.
(that would be the "brownian technology path" aka "soft machines" and not APM) - Self assembling foldamer systems do not crucially depend on life.
(there are several demonstrations that do without utilizing life's nanomachinery -- e.g. oglionucleotide DNA structures -- also the aforementioned engineering methodology chemistry is part of this)
Utilizing the molecular machinery of life to make shaped parts with atomic precision
Utilizing life's manufacturing systems is a standard technique by now (2017).
In living organisms the shaped parts are the proteins (small proteins are called peptides). These are chains of amino acid molecules which form a set of basic building blocks. (In this regard all life is equal.)
Note that there's a conflict of interest in the utilizing life's manufacturing machinery:
- In medicine one often wants shapes complementary to natural proteins (which's structure already have been resolved).
- In the context of bootstrapping for APM one is more interested in that the artificial parts mutually fit together in simple or more nontrivial ways. (E.g. similar to the self assembling capsid shells of virii).
Since this wiki is about APM we'll assume one is aiming for the latter (a non-medical structural application potentially useful for bootstrapping advanced APM). In that case the process works roughly like follows:
- "Backward engineering:" Determine the required sequence of amino acids such that the amino acid chain curls up into the desired shape (however this shape is determined (wiki-TODO: check specific papers)).
(Related: "inverse folding problem" and "de-novo protein engineering") - Digital encoding: Encoding the amino acid sequence into DNA base-pairs. (A simple straightforward trivial step.)
- Physical encoding: Synthesize the computer-generated DNA sequence to specification. (wiki-TODO: check details)
- Inserting: (This is the genetic engineering step.) Introduce the synthesized DNA into a host organism. There are several methods. One needs a "vector" to carry the (here fully man made) DNA past the organisms cells defense mechanisms. As organisms often some bacteria are chosen since they breed fast. (There are loads of details in this step e.g. knowledge about the various ways life and virii reproduce.)
- Breeding: Put the organisms in a nutrient solution and choose an optimal temperature. Naturally there are loads of things happening in the cells while growing and reproducing. Here is just the part that is most relevant for us. The part we are interested in most:
Transcription: translation of the protein encoding section of DNA (aka a gene) to messenger-RNA (mRNA). DNA is like the high security mass data storage of the cell while mRNA is like a short disposable working copy.
Translation: Assembly of A protein based on the information encoded in the messenger-RNA (mRNA)
Self-folding: Right after (or actually during) the synthesis of the protein it curls up and self folds to a shape.
- Extracting: Finally extract the desired protein out of the cells that made it and get them as pure as possible.
- Post processing: Control temperature over time in a precise manner to aid self assembly of (already self folded) proteins.
The intended product could e.g. be a 2D protein crystal.
- Analytics: Use various kind of (usually non optical) microscopes to check whether you actually made what you've intended to make.
Note that beside the core manufacturing of our desired protein there is also a much much longer string of other things going on. All the manufacturing for the reproduction of the organism and all the other subsystems of the organisms: energy, information, waste, ...)
So this is quite a process and the throughput of this isn't very high. Thus synthetic proteins currently (2017) are massively more expensive than raw biological products like e.g. food.
Far term outlook: A main goal of APM is (beside a switch to more stiff materials than bio-foldamers) to switch that around and make advanced gem-gum products at least as cheap as food (on a per mass basis).
Notes
Proteins (and foldamers in general) tend to have have weak bonds between folds thus they may only feature topological atomic precision especially on their outside. Some tightly packed proteins might feature positional atomic precision inside (e.g. ion channel proteins) (TODO: investigate this).
Related
External links
Wikipedia
- Protein_biosynthesis
- Protein_production (biotechnological)
- Cell-free_protein_synthesis
- Peptide_synthesis
