Why Do Protein Folding Rates Correlate with Metrics of Native Topology?

For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We sim...

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Detalles Bibliográficos
Autores: Faísca, Patrícia F.N., Travasso, Rui D. M., Parisi, Andrea, Rey Gayo, Antonio
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/42591
Acceso en línea:https://hdl.handle.net/20.500.14352/42591
Access Level:acceso abierto
Palabra clave:544
article
chemical structure
chemistry
computer simulation
kinetics
protein folding
protein tertiary structure
thermodynamics
Bioquímica (Química)
Química física (Química)
Descripción
Sumario:For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We simulate a large set of circular permutants, thus eliminating dependencies of the folding rate on other protein properties (e.g. stability). We show that the rate-contact order correlation is a consequence of the fact that, in high contact order structures, the contact order of the transition state ensemble closely mirrors the contact order of the native state. This happens because, in these structures, the native topology is represented in the transition state through the formation of a network of tertiary interactions that are distinctively long-ranged.