63273 20171129112116.0 doi 10.1371/journal.pcbi.1002647 sideral 78974 ART-2012-78974 eng García-Fandiño, R. Defining the Nature of Thermal Intermediate in 3 State Folding Proteins: Apoflavodoxin, a Study Case 2012 Access copy available to the general public Unrestricted The early stages of the thermal unfolding of apoflavodoxin have been determined by using atomistic multi microsecond-scale molecular dynamics (MD) simulations complemented with a variety of experimental techniques. Results strongly suggest that the intermediate is reached very early in the thermal unfolding process and that it has the properties of an “activated” form of the native state, where thermal fluctuations in the loops break loop-loop contacts. The unrestrained loops gain then kinetic energy corrupting short secondary structure elements without corrupting the core of the protein. The MD-derived ensembles agree with experimental observables and draw a picture of the intermediate state inconsistent with a well-defined structure and characteristic of a typical partially disordered protein. Our results allow us to speculate that proteins with a well packed core connected by long loops might behave as partially disordered proteins under native conditions, or alternatively behave as three state folders. Small details in the sequence, easily tunable by evolution, can yield to one or the other type of proteins. info:eu-repo/grantAgreement/ES/DGA/B89 info:eu-repo/grantAgreement/ES/MICINN/BFU2010-16296 info:eu-repo/grantAgreement/ES/MICINN/BIO2009-10964 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.867 2012 MATHEMATICAL & COMPUTATIONAL BIOLOGY 4 / 47 = 0.085 2012 Q1 T1 BIOCHEMICAL RESEARCH METHODS 11 / 74 = 0.149 2012 Q1 T1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bernadó, P. Ayuso-Tejedor, S. (orcid)0000-0002-2879-9200 Sancho, J. Universidad de Zaragoza Orozco, M. 1002 060 Universidad de Zaragoza Departamento de Bioquímica y Biología Molecular y Celular Bioquímica y Biología Molecular 8, 8 (2012), e10026 [15 pp] PLoS Comput. Biol. PLoS Computational Biology 1553-734X 1787310 http://zaguan.unizar.es/record/63273/files/texto_completo.pdf Versión publicada 130729 http://zaguan.unizar.es/record/63273/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:63273 articulos driver 2017-11-28-12:44:58 ARTICLE