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

ABSTRACT: A key question in protein studies is the proportion of amino acid sequences that correspond to functional proteins, often called protein rarity. This issue underlies the relationship between mutations and disease, theories on the origin of proteins, and strategies for engineering new proteins. Recent literature has detailed how to employ estimates of protein rarity to evaluate the required biasing of functional sequences in sequence space to allow for evolutionary paths to connect distinct proteins. One challenge in addressing rarity has been an imprecise definition of function and a lack of consistency in methodology. This study introduces a new methodology, referred to as PRISM, to evaluate protein rarity based on the impact of mutations on stability. PRISM offers a suite of methods that

SUBMITTER: Miller BJ 

PROVIDER: S-EPMC12747414 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature