The relationship between local frustration and protein function
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Updated: Oct 30, 2026

Time-Resolved Fluorescence Anisotropy from Single Molecules for Characterizing Local Flexibility in Biomolecules
Published on: April 25, 2025
César A Ramírez-Sarmiento1, Elizabeth A Komives2
1Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Av Vicuña Mackenna 4860, Santiago 7820436, Chile; ANID, Millennium Science Initiative Program, Millennium Institute for Integrative Biology (iBio), Av. Libertador Bernardo O'Higgins 340, Santiago 8331150, Chile.
Abstract:
Energy landscape theory is the accepted theoretical framework for understanding protein folding based on minimizing frustration. The theory provides an algorithm to learn the energy of amino acid interactions within a folded protein structure that also allows evaluation of localized regions of frustration. Most amino acid contacts are minimally frustrated or neutral, but patches of amino acid contacts are highly frustrated. These energetically unfavorable interactions are mostly found on the protein surface and have been linked to protein function in various ways. This review highlights experimental and computational exploration of how localized energetic frustration is linked to protein function.
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