Local energetic frustration conservation in protein families and superfamilies.

Autor: Freiberger MI; Laboratorio de Fisiología de Proteínas, Departamento de Química Biológica - IQUIBICEN/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina., Ruiz-Serra V; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain., Pontes C; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain., Romero-Durana M; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain., Galaz-Davison P; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine, and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, 7820436, Chile.; ANID - Millennium Science Initiative Program - Millennium Institute for Integrative Biology (iBio), Santiago, 8331150, Chile., Ramírez-Sarmiento CA; Institute for Biological and Medical Engineering, Schools of Engineering, Medicine, and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, 7820436, Chile.; ANID - Millennium Science Initiative Program - Millennium Institute for Integrative Biology (iBio), Santiago, 8331150, Chile., Schuster CD; Laboratorio de Bioinformática, Departamento de Química Biológica - IQUIBICEN/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina., Marti MA; Laboratorio de Bioinformática, Departamento de Química Biológica - IQUIBICEN/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EGA, Buenos Aires, Argentina., Wolynes PG; Center for Theoretical Biological Physics and Department of Chemistry, Rice University, Houston, TX, 77005, USA., Ferreiro DU; Laboratorio de Fisiología de Proteínas, Departamento de Química Biológica - IQUIBICEN/CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina., Parra RG; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain. gonzalo.parra@bsc.es., Valencia A; Computational Biology Group, Life Sciences Department, Barcelona Supercomputing Center, Barcelona, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Dec 16; Vol. 14 (1), pp. 8379. Date of Electronic Publication: 2023 Dec 16.
DOI: 10.1038/s41467-023-43801-2
Abstrakt: Energetic local frustration offers a biophysical perspective to interpret the effects of sequence variability on protein families. Here we present a methodology to analyze local frustration patterns within protein families and superfamilies that allows us to uncover constraints related to stability and function, and identify differential frustration patterns in families with a common ancestry. We analyze these signals in very well studied protein families such as PDZ, SH3, ɑ and β globins and RAS families. Recent advances in protein structure prediction make it possible to analyze a vast majority of the protein space. An automatic and unsupervised proteome-wide analysis on the SARS-CoV-2 virus demonstrates the potential of our approach to enhance our understanding of the natural phenotypic diversity of protein families beyond single protein instances. We apply our method to modify biophysical properties of natural proteins based on their family properties, as well as perform unsupervised analysis of large datasets to shed light on the physicochemical signatures of poorly characterized proteins such as the ones belonging to emergent pathogens.
(© 2023. The Author(s).)
Databáze: MEDLINE
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