A methodology for calculating the rarity of diverse proteins based on functional specificity and thermodynamic stability

Brian J. Miller · 2025

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Description

Brian Miller presents, in a 2025 methods paper, a cleaner way to estimate how rare working proteins are among all possible amino acid chains. That rarity underpins questions from disease mutations to the origin of proteins. Past estimates suffered from fuzzy definitions of function and uneven methods.

His suite, called PRISM, judges rarity through how mutations erode a protein's stability, using whichever stability data a given protein offers. The methods are simpler than older ones yet give sound upper bounds. Applied to several proteins, the numbers match earlier studies that found working sequences exceedingly rare. Uses in protein design, evolution, and disease work are sketched.

Catalog record

CREATORBrian J. Miller
YEAR2025
COLLECTIONPAPERS
FORMATTXT
FILE SIZE63 KB
VERSION1.0
LICENSECC BY 4.0
RIGHTSCC BY
SOURCEEurope PMC

Source: https://europepmc.org/articles/PMC12747414

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