Tractable molecular adaptation patterns in a designed complex peptide system

Molecular adaptation, robustness, and stochastic processes are characteristic of living systems, arising from the ability to distribute the impact of applied stress to huge numbers of covalent and noncovalent interactions in mixtures of molecules. The study of such behavior is difficult due to intractability of systems that have sufficient complexity to display these features. Herein, we create biomolecular complexity from the bottom up through selection of a chemical interaction space of mixtures of 5 or 15 dipeptides, which by reversible enzymatic sequence exchange produces 25 or 225 dynamically interacting tetrapeptides. Analysis of tetrapeptide sequence abundance leads to readily interpretable patterns. These reveal that a system with this degree of complexity is able to respond stochastically, self-organize and drive sequence selective oligomerization in response to changes in external conditions, and exhibit robustness by its ability to share the impact of an applied change of conditions over a multitude of interactions.