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How sticky are our proteins? Quantifying hydrophobicity of the human proteome

SUMMARY: Proteins tend to bury hydrophobic residues inside their core during the folding process to provide stability to the protein structure and to prevent aggregation. Nevertheless, proteins do expose some ‘sticky’ hydrophobic residues to the solvent. These residues can play an important function...

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Detalles Bibliográficos
Autores principales: van Gils, Juami Hermine Mariama, Gogishvili, Dea, van Eck, Jan, Bouwmeester, Robbin, van Dijk, Erik, Abeln, Sanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710682/
https://www.ncbi.nlm.nih.gov/pubmed/36699344
http://dx.doi.org/10.1093/bioadv/vbac002
Descripción
Sumario:SUMMARY: Proteins tend to bury hydrophobic residues inside their core during the folding process to provide stability to the protein structure and to prevent aggregation. Nevertheless, proteins do expose some ‘sticky’ hydrophobic residues to the solvent. These residues can play an important functional role, e.g. in protein–protein and membrane interactions. Here, we first investigate how hydrophobic protein surfaces are by providing three measures for surface hydrophobicity: the total hydrophobic surface area, the relative hydrophobic surface area and—using our MolPatch method—the largest hydrophobic patch. Secondly, we analyze how difficult it is to predict these measures from sequence: by adapting solvent accessibility predictions from NetSurfP2.0, we obtain well-performing prediction methods for the THSA and RHSA, while predicting LHP is more challenging. Finally, we analyze implications of exposed hydrophobic surfaces: we show that hydrophobic proteins typically have low expression, suggesting cells avoid an overabundance of sticky proteins. AVAILABILITY AND IMPLEMENTATION: The data underlying this article are available in GitHub at https://github.com/ibivu/hydrophobic_patches. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics Advances online.