Are natural proteins special? Can we do that?
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Updated: Feb 16, 2026

Using the Open-Source MALDI TOF-MS IDBac Pipeline for Analysis of Microbial Protein and Specialized Metabolite Data
Published on: May 15, 2019
Michael H Hecht1, Shlomo Zarzhitsky1, Christina Karas1
1Departments of Chemistry and Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
Abstract:
Natural proteins represent a minuscule fraction of possible sequence space. These very rare sequences display remarkable properties: They fold into many different stable structures, and perform a wide range of complex biological functions. These two considerations-rarity and functionality-may suggest that natural proteins are somehow special. Is this true? We address this question by exploring attempts to recapitulate the special structures and functions of natural proteins into sequences designed de novo.
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