Functional block construction kit approach
The idea is to create chemical reaction facilitating positional assembly kinematic loop by using a modular construction kit of reusable structural self assembled components/parts/blocks such that at least some separation of concerns in their structural behavior remain preserved. E.g. that the blocks don't remain individually exchangeable and addition and or subtraction of blocks disturbs the rest of the structure only minimally.
Given the limitations it is highly unlikely that a great separation of concerns in the function can be achieved. That is there is no way to exchange a block to get a desired change in function. It's rather a giant game of trial and error in a very big search-space. This is still far from deliberate positional control.
This is basically a static version of the more ambitious catalysis construction kit approach. That is: There is no active actuation.
Contents
Problems of this approach
A main issue is the that early loops suffer from incapability of proper separation of concerns in both
- their makeup and
- their function
Makeup:
E.g. in proteins sidechains compete for 3 different functions:
- cohesion (outside needs to be hydrophile, inside needs to be hydrophobe, otherwise no protein forms)
- definition of exterior complementary surfaces
- definition of external functions (fubctional group sidechains – tooltips so to say - sometines called fingers – bad misnomer see below)
Function:
To give an intuitive analogy: Side-chains of proteins behave a bit like wobbly slightly magnetic noodles under permanent shaking. They do not operate individually but holistically. One cannot just slot one out and another one in at a critical tooltip-spot without changing both its spacial configuration and all the configuration of all the sidechains in the local environment too. To make them stick and stay despite the shaking they need to be packed tightly with sidechains that pack for minimal wiggleroom. The possibility space quickly gets hyper-astronomically big.
Floppy fingers or fat fingers, pick your poison
A fingers purpose is to stably point to something on its own.
So naming side-chains fingers seems like a bit of a misnomer.
If anything it's a sloppy finger.
What can stably make a shape is a whole bunch of side-chains when they are well and tightly packed.
That is also barely callable a finger because it's not sharp and pointy like a finger. If anything it's a fat finger.
This is perhaps what Richard Smalley was thinking about when putting out his fat finger problem critique.
(That diamondoid tips do not suffer from fat finger problem to a crippling degree should be pretty obvious.)
Fancy stiff fingers
Adding in special unnatural side-chains that are stiffer due to them containing more polycyclic elements is a theoretical option. But ...
- there is still no complete decoupling from the local environment, just less so
- even if more decoupled there is still barely any control for orientation (pose)
- this limits one to abiotic peptide synthesis – (expensive, only short strands, no "randomization for free")
- lack of randomization limits the playability of the giant game of trial and error mentioned in the intro.
A question naturally popping up is:
- conventionally synthesized long peptides and
- abiotically synthesized short peptides
can these be combined to get the best of both worlds?
