Random peptides rich in small and disorder-promoting amino acids are less likely to be harmful.

ABSTRACT: Proteins are the workhorses of the cell, yet they carry great potential for harm via misfolding and aggregation. Despite the dangers, proteins are sometimes born de novo from non-coding DNA. Proteins are more likely to be born from non-coding regions that produce peptides that do little to no harm when translated than from regions that produce harmful peptides. To investigate which newborn proteins are most likely to "first, do no harm", we estimate fitnesses from an experiment that competed Escherichia coli lineages that each expressed a unique random peptide. A variety of peptide metrics significantly predict lineage fitness, but this predictive power stems from simple amino acid frequencies rather than the ordering of amino acids. Amino acids that are smaller and that promote intrinsic

SUBMITTER: Kosinski L 

PROVIDER: S-EPMC9210321 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature