The Otto research group studies how simple building blocks — in this case a nucleobase linked to the amino acid aspartic acid — can form rings. In previous research, Otto has shown that such rings can form stacks which can grow and divide, and show a level of chemical evolution. But this time, something different happened. Otto: ‘One of my PhD students, Bin Liu, noticed that very large rings were formed, polymers of 15 building blocks.’ They were extremely stable, so eventually most of the building blocks were transformed into these rings.
After studying the rings’ structure with X-ray crystallography, it became clear to the team that they were folded. ‘When rings form stacks, there is interaction between the molecules. In this case, the interaction took place within the large molecule.’ The hydrophobic parts of the ring were folding into the centre of the molecule, which is also what happens with proteins in water. The folding pattern, however, is completely different. ‘Proteins are polymers linked by amine bonds. In our molecules, the building blocks are linked exclusively by disulphide bonds. The difference in structure results in a different folding pattern.’
This is the first time that a complex folding structure (or foldamer) that is so radically different from proteins has been described. ‘Despite decades of research, we still have no reliable design rules that can fully predict the folding of proteins’, explains Otto. This hampers the design of new enzymes. A different class of folding molecules can help us to understand the basic rules of molecular folding. ‘Furthermore, the molecule we describe in our paper is only the first that we’ve discovered. In the past year, we have discovered several more and will publish these later.’ …
A striking conclusion drawn from the discovery of this new folding molecule is that complexity can emerge spontaneously. ‘This is interesting for origin-of-life research: apparently, you can get these complex molecules before biological evolution has started.’ The formation of the new molecule is actually driven by folding, explains Otto. ‘That is quite special. The energy level of this molecule is very low. This drives the equilibrium from a “random” mixture of small rings towards this specific very stable 15-mer.’ Paper. (open access) – Bin Liu, Charalampos G. Pappas, Ennio Zangrando, Nicola Demitri, Piotr J. Chmielewski, Sijbren Otto. Complex Molecules That Fold Like Proteins Can Emerge Spontaneously. Journal of the American Chemical Society, 2019; DOI: 10.1021/jacs.8b11698 More.
A reader comments, “It isn’t very different from a crystal. That is, it forms complex shapes without evolution or design. But how many of these structures would have formed in nature in the absence of the researchers? We need to know that before we decide if this is relevant to the origin of life.”
In short, it’s geometry. But what follows?
See also: Claim: Complex Self-Replicating Molecules Can Emerge Spontaneously And Relatively Easily From Simple Chemical Reaction Systems If life can “emerge spontaneously and relatively easily from simple chemical reaction systems through a sequence of transitions,” why don’t we ever see it happening today?
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