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Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins

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The number of existing protein sequences spans a very small fraction of sequence space. Natural proteins have overcome a strong negative selective pressure to avoid the formation of insoluble aggregates. Stably folded globular proteins and intrinsically disordered proteins (IDP) use alternative solutions to the aggregation problem. While in globular proteins folding minimizes the access to aggregation prone regions IDPs on average display large exposed contact areas. Here, we introduce the concept of average meta-structure correlation map to analyze sequence space. Using this novel conceptual view we show that representative ensembles of folded and ID proteins show distinct characteristics and responds differently to sequence randomization. By studying the way evolutionary constraints act on IDPs to disable a negative function (aggregation) we might gain insight into the mechanisms by which function - enabling information is encoded in IDPs.

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NARANJO, Yandi, PONS VALLÈS, Miquel, KONRAT, Robert. Meta-structure correlation in protein space unveils different selection rules for folded and intrinsically disordered proteins. _Molecular Biosystems_. 2012. Vol. 8, núm. 1, pàgs. 411-416. [consulta: 21 de gener de 2026]. ISSN: 1742-206X. [Disponible a: https://hdl.handle.net/2445/47843]

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