Seeking Precise Protein-like Functions from Random Heteropolymer Ensemble and through Dimensionality Reduction

作者：Guangqi Wu, Tianyi Jin, Haisen Zhou, Connor W. Coley, Alfredo Alexander‐Katz, Hua Lu · 发表于：ACS Central Science · 年份：2025 · DOI：10.1021/acscentsci.5c01382 · 被引用次数：9 · 研究领域：Chemical Synthesis and Analysis、Protein Structure and Dynamics、Machine Learning in Bioinformatics

Proteins achieve diverse biological functions through precise sequence-structure relationships, yet they can also function through statistical ensembles rather 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 to function 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 and mechanistic understanding of functional RHPs, emphasizing their emergent behaviors and utility across sustainability, human health, and pharmaceuticals. We discuss how autonomous experimentation, machine learning, and multiscale modeling are converging to accelerate design and discovery in this vast chemical space. By embracing statistical design principles, we propose a new framework for creating functional polymers that mirror biological systems.