James Tour and his 60-day challenge

[Rumraket (Mikkel R.)]

Let me bring everyone’s attention to this new paper:

New interesting paper on biorxiv on protein evolution from repeats of small peptides

https://www.biorxiv.org/content/10.64898/2025.12.04.691947v1.full Turns out new AI-based structure prediction tools can now corroborate the long-standing hypothesis that protein folding structures are much easier to evolve from repeats of smaller peptides, than entirely random amino acid sequences. Conclusions Our results show that the inclusion of repeats enriches the fraction of otherwise random sequences that can adopt folded conformations. With repeat lengths of 5 to 20 residues, over 1% of the sequences are predicted to fold, mostly into repeating solenoids or β-hairpins, although we also observe helical bundles and tightly wound helical screws that represent a new family of super-secondary structures. With the inclusion of INDELs between blocks of repeats, we also observe the formation of helical bundles at a frequency of 0.5 to 1%. On the other hand, beyond a repeat length of 30 residues, the frequency of observing predicted folded structures decreased sharply, reaching 0.00…

What I also find significant and relevant is how common the DNA replication machinery accidentally creates repeats. Relatively short amino acid repeats are surprisingly likely to yield foldable proteins, and the DNA replication process is very prone to create small repeats. It is almost as if the two factors work together to facilitate protein evolution.

Were I a religious man I might have suspected the laws of physics were fine tuned to make evolution unavoidable.