Difference between revisions of "Thermally driven self assembly"
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* [[self finding]] | * [[self finding]] | ||
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| − | * [[iterative self-assembly]] | + | * [[iterative self-assembly]] (in-vitro superpower) |
* [[one-pot self-assemby]] (necessarily requiring a larger size of an orthogonal set of interfaces) | * [[one-pot self-assemby]] (necessarily requiring a larger size of an orthogonal set of interfaces) | ||
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{{wikitodo|what are the overlaps and differences}} <br> | {{wikitodo|what are the overlaps and differences}} <br> | ||
{{wikitodo|what are advantages and limitations}} | {{wikitodo|what are advantages and limitations}} | ||
| + | |||
| + | == Challenges == | ||
| + | |||
| + | === What is progress in self assembly capabilities === | ||
| + | |||
| + | * Advancednedd of self-assembly is about address space size | ||
| + | * Advancedness of self assembly is not about plain size | ||
| + | |||
| + | Size of self assembled structure is not a good measure for the advancedness of ones artificial | ||
| + | self assembly technology. The same goes for self assemblies that go around 360° full circle. | ||
| + | |||
| + | When all parts have an identical self matching shape then | ||
| + | this gives ride to infinite translatory or rotatory symmetries. | ||
| + | |||
| + | What really counts for judging the advancedness is the size of fully and arbitrarily addressable space. | ||
| + | |||
| + | === In structural DNA nanotechnology === | ||
| + | |||
| + | First level self assembly of DNA staple bricks to DNA blocks: | ||
| + | * Yields drop quickly with size | ||
| + | * addressable space is finite due to staple strands of suitable length only capably of carrying a few bits of info | ||
| + | |||
| + | Second level self assembly of pre-self-assembled DNA blocks to multiblock structures: | ||
| + | * Bigger blocks diffuse more slowly | ||
| + | |||
| + | In case of 3D DNA blocks there is [[redundant access self-assembly]] involved | ||
| + | contributing to the robustness of the process. | ||
| + | |||
| + | === In case of de-novo protein engineering === | ||
| + | |||
| + | Of most interest as basic reusable building bricks are <br> | ||
| + | the most predictably folding and most robust protein structures <br> | ||
| + | that come closest to prismatic brick shapes. Helices and sheets. | ||
| + | |||
| + | What one wants is both: | ||
| + | * high specificity (wrong interface pairings don not stick and hold together well) | ||
| + | * high affinity (right interfaces do fit and hold together well) | ||
| + | What one wants to design is a '''multi-orthogonal set of interface pairings'''. <br> | ||
| + | One can chart a matrix listing the strengths of all possible interface pairings. | ||
| + | |||
| + | In case of proteins the side-chains already fulfill the purpose of | ||
| + | defining the proteins shape (how the backbone is supposed to fold) | ||
| + | Redirecting too many of them to define an outward facing inter-protein interface instead | ||
| + | can start destabilizing the proteins shape itself. | ||
| + | |||
| + | Potentially destabilizing factors: | ||
| + | * putting too many side chains to use to define an outerinterface | ||
| + | * putting too many side chains of similar polarity adjacently | ||
| + | * putting too many hydrophobic side chains outward | ||
| + | * putting too many side chains to other use (for some specific applications) | ||
| + | |||
| + | All together this results in that (in the case of proteins) | ||
| + | the size of the sets of achievable "good" orthogonal interfaces is rather very small. | ||
| + | Countable on one hand. | ||
| + | |||
| + | So only very small assemblies can be achieved via [[one-pot assembly]]. | ||
| + | For a bit bigger addressable spaces iterative self-assembly is needed. | ||
| + | This cannot be done directly in protein synthesizing cells though, | ||
| + | which would provide some protein folding help (via the chaperone folding helper proteins). | ||
| + | |||
| + | In iterative self-finding self-assembly of protein blocks the assembly happens in a linear that is branchless sequence. | ||
| + | In the case of protein blocks the product structure is not necessarily geometrically linear and not necessarily flexible). | ||
| + | |||
| + | In a linear assembly sequence failure rates multiply with each iterative self-assembly step. | ||
| + | Much like failure rates multiply up in the case of the synthesis of foldamer chain molecules. | ||
| + | So even iterative self assembly hits its limits soon. | ||
| + | |||
| + | [[Redundant access self-assembly]] seems to be able to avoid the problem with the multiplying error rates. | ||
| + | But this would probably need some amount of one pot assembly? {{todo|investigate here}} | ||
| + | |||
| + | Maybe maybe enough structure could be encoded via 2nd level iterative self assembly such that | ||
| + | a 3rd level one pot self assembly becomes possible. | ||
| + | |||
| + | '''Foldamer in foldamer inset:''' | ||
| + | |||
| + | Given all this trouble with the scaling de-novo protein self-assembly outlined above: | ||
| + | It might be easier to integrate/embed just somewhat scaled de-novo protein engineering into | ||
| + | a stuctural DNA nanotechnology framework surrounding it. | ||
| + | Compensating the massive drop in stiffness by a sufficiently large interface area between the foldamer technologies. | ||
== Related == | == Related == | ||
Revision as of 04:34, 16 March 2021
Thermally driven assembly is also called called self assembly or brownian assembly (seldom)
(TODO: Add minimal definition)
- Today thermally driven assembly is already extensively used (e.g. structural DNA nanotechnology) this will continue onward into the early stages of the development of atomically precise manufacturing (APM).
- In the early and the later stages of APM development: brownian mechanosynthesis could be an intermediate step to advanced APM systems.
- In the later and the final stages of APM development: self assisted assembly will come to intensive use.
Beside the actual function of the building block (structural element / machine element) completely unguided thermally driven assembly requires the building blocks to be have a unambiguous unique puzzle piece shape that completely determines its target position. (everything that can stick will stick)
- Brownian assembly is generally slower then advanced directed assembly like mechanosynthesis. (numbers needed)
- The ambient temperature dictates diffusion speed.
- Lower dimensionality that is diffusion on a surface instead of a volume or on a line instead of a surface speeds up the process.
- Dividing one long diffusion path to several shorter irreversible diffusion transport stretches speeds up the process.
Contents
Possible sub-classifications
- iterative self-assembly (in-vitro superpower)
- one-pot self-assemby (necessarily requiring a larger size of an orthogonal set of interfaces)
- self-assembly of floppy foldamer chains at the first selfassembly level
- self-assembly of stiff pre-self-assembled tiles at the second selfassembly level
(wiki-TODO: what are the overlaps and differences)
(wiki-TODO: what are advantages and limitations)
Challenges
What is progress in self assembly capabilities
- Advancednedd of self-assembly is about address space size
- Advancedness of self assembly is not about plain size
Size of self assembled structure is not a good measure for the advancedness of ones artificial self assembly technology. The same goes for self assemblies that go around 360° full circle.
When all parts have an identical self matching shape then this gives ride to infinite translatory or rotatory symmetries.
What really counts for judging the advancedness is the size of fully and arbitrarily addressable space.
In structural DNA nanotechnology
First level self assembly of DNA staple bricks to DNA blocks:
- Yields drop quickly with size
- addressable space is finite due to staple strands of suitable length only capably of carrying a few bits of info
Second level self assembly of pre-self-assembled DNA blocks to multiblock structures:
- Bigger blocks diffuse more slowly
In case of 3D DNA blocks there is redundant access self-assembly involved contributing to the robustness of the process.
In case of de-novo protein engineering
Of most interest as basic reusable building bricks are
the most predictably folding and most robust protein structures
that come closest to prismatic brick shapes. Helices and sheets.
What one wants is both:
- high specificity (wrong interface pairings don not stick and hold together well)
- high affinity (right interfaces do fit and hold together well)
What one wants to design is a multi-orthogonal set of interface pairings.
One can chart a matrix listing the strengths of all possible interface pairings.
In case of proteins the side-chains already fulfill the purpose of defining the proteins shape (how the backbone is supposed to fold) Redirecting too many of them to define an outward facing inter-protein interface instead can start destabilizing the proteins shape itself.
Potentially destabilizing factors:
- putting too many side chains to use to define an outerinterface
- putting too many side chains of similar polarity adjacently
- putting too many hydrophobic side chains outward
- putting too many side chains to other use (for some specific applications)
All together this results in that (in the case of proteins) the size of the sets of achievable "good" orthogonal interfaces is rather very small. Countable on one hand.
So only very small assemblies can be achieved via one-pot assembly. For a bit bigger addressable spaces iterative self-assembly is needed. This cannot be done directly in protein synthesizing cells though, which would provide some protein folding help (via the chaperone folding helper proteins).
In iterative self-finding self-assembly of protein blocks the assembly happens in a linear that is branchless sequence. In the case of protein blocks the product structure is not necessarily geometrically linear and not necessarily flexible).
In a linear assembly sequence failure rates multiply with each iterative self-assembly step. Much like failure rates multiply up in the case of the synthesis of foldamer chain molecules. So even iterative self assembly hits its limits soon.
Redundant access self-assembly seems to be able to avoid the problem with the multiplying error rates. But this would probably need some amount of one pot assembly? (TODO: investigate here)
Maybe maybe enough structure could be encoded via 2nd level iterative self assembly such that a 3rd level one pot self assembly becomes possible.
Foldamer in foldamer inset:
Given all this trouble with the scaling de-novo protein self-assembly outlined above: It might be easier to integrate/embed just somewhat scaled de-novo protein engineering into a stuctural DNA nanotechnology framework surrounding it. Compensating the massive drop in stiffness by a sufficiently large interface area between the foldamer technologies.
Related
- Thermal motion
- Diffusion transport
- Thermally driven assembly is a powerful for bootstrapping in the incremental path towards advanced APM. It can help the introduction of total positional control
- In thermally driven assembly diffusion transport brings the parts to their final destination.
- In the process of self folding the parts are already connected (assembled) on a common flexible backbone but there is further thermally driven folding happening. This may be counted to thermally driven assembly but is often not.
- Brownian technology path
- Kinetic traps
External links
There's huge amount of literature on thermally driven assembly.
