Chem
Volume 8, Issue 7, 14 July 2022, Pages 1894-1905
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Article
Tractable molecular adaptation patterns in a designed complex peptide system

https://doi.org/10.1016/j.chempr.2022.03.016Get rights and content
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Highlights

  • Enzymatic exchange of mixtures of dipeptides leads to buildup of tetrapeptides

  • Mixtures of 15 dipeptides lead to 225 tetrapeptides that can be tracked using LCMS

  • Self-organization can drive selective peptide sequence buildup

  • Increased compositional complexity increases robustness

The bigger picture

The building blocks and design strategies of life can be used to create materials with advanced functionalities that exceed those of synthetic materials. Despite progress, it is still a mystery how the assembly and self-organization of the 20 amino acids that make up proteins ultimately give rise to functional matter. Our approach is to learn about complexity and emergence in the biological design space by building it. By selecting collections of interacting dipeptides that can exchange to form longer peptides by recombination and exchange, we can track them individually and collectively. The approach provided insights about how chemical systems create patterns of self-organization. We envisage that the insights will translate to design concepts for sensors, catalysts, and energy conversion that are not restricted to the designs or conditions used in biological evolution, enabling the repurposing “chemistry-of-life” building blocks and processes for green materials and technology.

Summary

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.

UN Sustainable Development Goals

SDG12: Responsible consumption and production
SDG15: Life on land

Keywords

adaptation
complexity
systems chemistry
peptide mixtures
order disorder

Data and code availability

All data are available in the main text or the supplemental information.

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