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  • https://doi.org/10.1021/acscentsci.5c01382Copy DOI Icon

Seeking PreciseProtein-like Functions from RandomHeteropolymer Ensemble and through Dimensionality Reduction

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Abstract

Proteins achieve diverse biological functions throughprecise sequence-structurerelationships, yet they can also function through statistical ensemblesrather than as individual, static entities. Inspired by this paradigm,recent work has explored random heteropolymers (RHPs) as synthetic,scalable, and versatile protein mimetics. RHPs have been found tofunction as polymer ensembles capable of folding, binding, catalyzing,and stabilizing biomolecules with control over the monomer sequence.In this Outlook, we highlight recent advances in the discovery andmechanistic understanding of functional RHPs, emphasizing their emergentbehaviors and utility across sustainability, human health, and pharmaceuticals.We discuss how autonomous experimentation, machine learning, and multiscalemodeling are converging to accelerate design and discovery in thisvast chemical space. By embracing statistical design principles, wepropose a new framework for creating functional polymers that mirrorbiological systems.

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