Self Replicating molecules

Hi AllI found an article which may be of interest if you can access it.Journal of the American Chemical Society
Vol. 124, No. 24 June 19, 2002
Approaching Exponential Growth with a Self-Replicating Peptide
Roy Issac and Jean Chmielewski pp 6808 - 6809The abstract is:---------Self-replicating peptide systems hold great promise for a wide range of technological applications, as well as to address fundamental questions
pertaining to the molecular origins of life. The development of self-replicating compounds capable of high efficiency, however, has remained elusive.
Here we disclose a successful strategy whereby modulation of coiled-coil stability results in remarkable catalytic efficiency for self-replication. By shortening the peptide to the minimum length necessary for coiled-coil formation a highly efficient self-replicating system was obtained due to very low background reaction rates, bringing the efficiency close to naturally occurring enzymes.-----------The system consists of two different short polypeptide chains (13 and 14 amino acids long) which naturally adopt a helical conformation which can be joined to produces a longer peptide. Three longer peptide chains will spontaneouly aggregate into a trimer, which then binds one of each of the two shorter chains and causes them to join together to form a fourth long peptide. One long peptide dissociates from the complex and the catalytic trimer is reformed.On the upside the sequences are completely designed by humans, so you can't argue that they are just a copy of divine origin. They also only contain five different amino acids, which simplifies things. One of the peptide chains is chemically activated though (with a reactive thioester group) so the dice are definitely loaded energetically. It does nicely demonstrate the principle of self replicating molecules though and the kinetics are almost as efficient as real enzymes.This is undoubtedly a simple and idealised system. I think a historical perspective is required though. Do we look back on the simple experiments of Newton as inadequate and incomplete foundations for his theories or do we admire his vision and determination? You may argue that scientists are nowhere near demonstrating that abiogenesis ever took place, but can you argue that this isn't a step in the right direction?Shane

My worry is not about what is or is not man-made but that the snthesis would proceed with Fihsher's version over Wright's sided view with Muller and Plunkett. It is possible to create even something worse than junk, trash or garbage.

Yes this is fascinating stuff. As an ex-peptide person (I used to work on peptide toxins) I am aware of this but it is also extremely clear that this could (i) not systematically replicate an arbitary sequence (it only works for coiled-coils) and (ii) is not related to the way in which DNA replicates. Perhaps this will become known as the coiled-coil world (ala the RNA world)?

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Originally posted by Tranquility Base:
Yes this is fascinating stuff. As an ex-peptide person (I used to work on peptide toxins) I am aware of this but it is also extremely clear that this could (i) not systematically replicate an arbitary sequence (it only works for coiled-coils)

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Does the article not claim that the molecules spontaneously adopt a helical structure? I take that as coiled. I know I don't have to ask you to correct me if I'm wrong.

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and (ii) is not related to the way in which DNA replicates. Perhaps this will become known as the coiled-coil world (ala the RNA world)?

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Why does this have to replicate the way DNA replicates? As I understand it, DNA could be a late comer in the game.------------------
http://www.hells-handmaiden.com

The point is that arbitrary DNA seqeunces replicate (via a host of enzyme systems). Peptides will not - only a few special sequences will. It's fascinating (I've been kicking myself ever since for not thinking of it) but it's not a systematic replication system.[This message has been edited by Tranquility Base, 07-29-2002]

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Originally posted by Tranquility Base:
The point is that arbitrary DNA seqeunces replicate (via a host of enzyme systems). Peptides will not - only a few special sequences will. It's fascinating (I've been kicking myself ever since for not thinking of it) but it's not a systematic replication system.

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And?------------------
http://www.hells-handmaiden.com

No-one has outlined how one can go from a self replicating peptide to a cell! I thought this was a CvsE BBS?

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Originally posted by Tranquility Base:
No-one has outlined how one can go from a self replicating peptide to a cell!

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There is a lot that has not been done. There are gaps in knowledge. I have seen some good starts at it though.You can't jump from 'no one has done it' to 'it can't be done'. Your problem is to prove that it cannot be done, and that it cannot be done any other way.Its just chemistry, TB. There is nothing magical about it.

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I thought this was a CvsE BBS?

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Are we not discussing creation?------------------
http://www.hells-handmaiden.com

What are the attributes of the threshold between molecules that don't self-replicate, and those that do? This threshold must have some local charge morphology or charge gradient basis (I speculate). Are there known phenomena at work?

I don't think you can readily define a threshold between molecules that self replicate and those that don't- its only a matter of efficiency and how picky they are about their environmental requirements for replication. It is a high dimensional problem so any "interfaces" will be necessarily fuzzy.

In the case of the coiled coil peptides I fully understand how the self replication works - it is not a mystery and it is very clear that it will only work for special seqeunces that fold into coiled coils.The coiled coils we are talking about are (eg) homodimeric (ie a two molecule coil with each molecule the same) that associates (binds) due to self-affinity in a symetric manner presumably.The key point is that becasue the molecule binds to itslef strongly it will probably also bind to the component amino-acids weakly. So that means that a single molecule of the peptide will bind to amino-acids floating around. These amino-acids will be briefly held near to each other in the correct sequence and cause a weak catalytic enhancement of spontaneous peptide bond formaiton joining two amino-acids together. This 'dipeptide' (two amin-acids) will now probably bind to the full peptide more strongly and make it more easy to get the next amino-acids to bind in seqeunce and catalytically bond. Eventaully the whole peptide will have replicated itself by this means. This is my understanding of how it works, it makes snese and it is presuamably the thinking that suggested the experiment. But it wil onyl work for coiled coil sequences that have enough self binding affinity and sequence specific selectivity. DNA replication does not require the DNA seqeucne to form any particular structure (like a coiled coil) - the double spirial helix is not important for replicaiton per se - it is the fact that A likes to bind to T and G to C. And all DNA coils anyway. Only very few peptides from cioiled coils. The peptide issue only works becasue the peptide sequence is somehow complementary to itself due to 3D structure and sequence.Please correct me anyone if that is not how it works.[This message has been edited by Tranquility Base, 07-31-2002]

Thanks for the reply. There has to be some thermodynamic solution that works in certain molecular configurations and charge gradients (environments) because we know DNA works. Salt doesn't replicate itself. it just precipitates out of solution. Between the two is a vast thermodynamic landscape. I was asking for some "signposts". The fundamental quantum mechanical phenomena are already known, just not how they apply in this case. For example, I personally had a suspicion that certain metals retained a spin state because of their bonding configuration in biological molecules when their subshells participated in binding sites. This spin state could be a factor in determinine when an enzyme acted, when DNA unfolded, etc.We saw self-ordering in our lab in simple nickel lattices and believe it has to do with strain between crystal structure planes changing the bond lengths and angles between the lattice atoms. This might also be predicted by band models now, however our results were in advance of mainstream theory. So, I am trying to learn about what TB said using solid-state work as a starting point. There is an answer to this in physical chemistry. It is a bad idea to bet against physicists.[This message has been edited by axial soliton, 08-02-2002]

The salt example is an excellent analogy of how simple self replication can be when you consider that a salt crystal can act as a nucleus for crystallisation in a supersaturated solution. Life by analogy is a vastly more complicated crystallisation/coalesence that occurs in a system where a thermodynamic gradient exists and a starting structure (seed/spore etc) is present which can tap into that energy is present also.I think the signposts to what is self replicating and what is life will be arbitrary. You only have to consider the unresolved issue of whether or not viruses are worth considering alive. The virus example is a good point as it requires a very complex biological environment in which to behave in a manner akin to life. In the peptide example I posted you also need a specific environment where the appropriate conditions and substrates are present. I think the sign posts will be arbitrary because it is a simple thought experiment to take a living cell and limit its complexity in a step wise manner where every loss of a function places limitations on the environment in which it can survive. For example you could remove its capacity to synthesise the amino acid tryptophan, placing a limitation on its environment to one that contains sufficient exogenous tryptophan. This process can be extended endlessly until the cell IS the environment.Shane

Arbitrary! For me, that word really blasts through in your message. There has to be some underlying system to this. Maybe it is the worst type of many-body problem, but why not break the phenomena at work here into pieces by time and type. Following what you said, viruses might be the minimalist entity one gets to when minimizing the complexity of cells. Maybe today's viruses are the spores of some extinct cells that have themselves evolved through natural selection because evolved cells endowed the viruses with modified base pairs now and then (freely associating here).I'm in a learning situation here, but arbitrary is hard to take. It is easier to find data to joust with creationists in every other technology field, it seems, than this one. It doesn't look like any creationists are readily offering their types of opinions here, and one of them keeps flaming out, so maybe we can just proceed without them.Carbon is the base molecule for life as we know it. Each of its idiosyncrasies are tools that can be used to figure out why self-replicating molecules make dopplegangers. What I think I know is that the 2p carbon subshell bonds covalently with other carbons. Nothing else does that. Not even silicon (sorry Horta). It is a light atom. Ionization energy of the 2p electron is 11ev. There is an unusual range of bond angles and lengths that are stable for carbon. Hybridization of orbitals is endemic. I feel this is due to the shape of the subshell compared to the number of nucleons, 6 neutrons and 6 protons. The diameter of carbon is the smallest of the series on the table at 0.15nm. Lithium, Beryllium, and Boron, are all larger with fewer electrons. The 2p subshell is non-magnetic and this matches psi^2 predictions for lobe size and shape. Hexagonal lattice structure seems to be the preferred one for carbon. Carbon can bond with any element not inert. Carbon is made early in the life of suns, so it is plentiful in the Universe. Though not a metal, some forms of carbon superconduct at room temperature and higher (we achieved 10^8A/cm^2, sustained from a multi-walled carbon nanotube. Absolutely incredible to see. Just incredible.). Other forms of carbon have a wide band-gap and do not conduct.I almost hate to mention this, because of the baggage, but carbon has 6 protons, 6 electrons, and 6 neutrons. If I spread the numbers out, it won't be discovered with a text search. I am thinking that the nucleus also has a-polar orbitals due to this pair of sextets. The implied hexagonal duet of nucleons could have interesting shape qualities in that 6 circles of one size fit in a plane precisely around a void having the same diameter as the circles. This happens exactly once in the range of geometry.What else is important about carbon? It forms graphene sheets readily. Is it also a catalyst for some biological interactions? Is there a relationship between carbon and the helicity of DNA? When DNA folds, there must be strained bonds at the folds. Are there carbon atoms there? Would it help to compare the de Broglie wave length of subshell electrons to bond length? That might help where the morphology of a receptor area on an enzyme couples to something. Maybe metal ions in a chain can be strained enough to be magnetic. Polaiity could determine whether coupling between molecules fits, or not.If some first-order rules can be hacked out, it is at least a first step.

What I am doing is to look at these replications as electromotive sources posssibly but so far using Pascal I have only got an outline of the chapters and some content not providedDedication- to Amy McCune who had the notion to to question if we can yet speak of the gene and signed on as advisor for an independent study on Croizat from which this writing began to take conventional shape.1Prima Facie Proposition and Plurivocal Definitions2 Form-making by Translation in Space (Maxwell's electric translation and magnetic rotation introduces the electrotonic displacment co-ordinates as a biological subset of vicariance biogeography under ontogenic laws of growth vicariantly (two removes from any reciprocal influence) during at most electro-pollution bioassay creation as Descartes is no Chinese.3 Ideal Plane in Panbiogeography - expts, models and database structures4 History, Baseline, and Centers @ Origins5 Mapping Standards and Individual Track Claims Ordinal thouhts6 Vicariance and Actual Individual Track Claims (relevance of panbiogeography to biology as a whole)7 Use of Vicariance Biogeography as an Interval to Spell fears of nanotechnology linked to whatever truth is in neophenogenesis( electrotonic displacement coordinated with neophenogenesis for any all other neophenogenic velocity (De Beer outlined) and force (beyond Hardy Weinberg equilibrium)8 Croizat and Post-Modernism9 Ecosystem Engineering ( water balance calculation under locomotions)10 Empirical Sentence Standard11 Philosophy of Vicariant Time - Reducing Provine's two Wright Landcapes to one by supplementing perversions turning Gibbs into more MacroThermodynamcis through irreversibilities of behaviorally insignificant energetically behaviors quantities any kind pigen holeable to orthogenesis of DIFFERENT steady morions no matter the orthoselection arguable between Fisher and Wright as minimum pressure (even in non-linear and non-equilibrium regimes) is not SMALL CONTINIOUS EFFECTS d e f i n ition ally as catastrophes could punctuate this space that sees more chemsity where I READ physics12 Spatial Evolution13 Nano-Ecology (techonology)14- Deviations from Maxwell's sphere (the case of e-fish) no matter the fractal # mediation of Pascal - Chinese projection in or of any ideal plane through changes at least in heterogenous equilibira (dissipative or not) and various technical means to achieve OTHER than subtraction of passage beyond infinite division (Feynamn's Maxwell etc) and conditions to terminate Provines critcism of Wright (paramters for isolation by distance etc) with transpiration, ontogeny recapitulates phylogeny becasue browninan motion is not mututally reciprocally independent of gravity fall and other virial/repulsion (action at a distance sets) in every Darwinization of Gladyshev's call -- future of all neo-darwinisms in the larger mendel ratio (mendelism(s)) controversy kept up by creationists especially over the correlation but not because still it is highly plausible until neophenogeneis be judged on this expanded physical descriptin extension basis.15 XeX- How the deduction happens. Criticism of Quine. An economics for theoretical biology of the symbol scriptures.