Local energetic frustration conservation in protein families and superfamilies

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...

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Detalles Bibliográficos
Autores: Freiberger, Maria I., Ruiz Serra, Victoria, Pontes, Camila, Romero Durana, Miguel, Galaz Davison, Pablo, Ramírez Sarmiento, Cesar A., Schuster, Claudio D., Marti, Marcelo A., Wolynes, Peter G., Ferreiro, Diego U., Parra, Gonzalo, Valencia, Alfonso|||0000-0002-8937-6789
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/401500
Acceso en línea:https://hdl.handle.net/2117/401500
https://dx.doi.org/10.1038/s41467-023-43801-2
Access Level:acceso abierto
Palabra clave:COVID-19 (Disease)
Protein sequencing
Energetic local frustration
Protein families
SARS-CoV-2
Simulació per ordinador
COVID-19 (Malaltia)
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
Descripción
Sumario: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.