RT Journal Article
T1 Defining the Nature of Thermal Intermediate in 3 State Folding Proteins: Apoflavodoxin, a Study Case
A1 García Fandiño, Rebeca
A1 Bernadó, Pau
A1 Ayuso Tejedor, Sara
A1 Sancho, Javier
A1 Orozco, Modesto
K1 Apoflavodoxin
K1 Folding Proteins
AB The early stages of the thermal unfolding of apoflavodoxin have been determined by using atomistic multi microsecondscale molecular dynamics (MD) simulations complemented with a variety of experimental techniques. Results stronglysuggest 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 unrestrainedloops 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 inconsistentwith a well-defined structure and characteristic of a typical partially disordered protein. Our results allow us to speculatethat proteins with a well packed core connected by long loops might behave as partially disordered proteins under nativeconditions, or alternatively behave as three state folders. Small details in the sequence, easily tunable by evolution, can yieldto one or the other type of proteins
PB Plos
SN 1553-7358
YR 2012
FD 2012
LK http://hdl.handle.net/10347/22211
UL http://hdl.handle.net/10347/22211
LA eng
NO García-Fandiño R., Bernado, P., Ayuso-Tejedor, S., Sancho, J. y Orozco, M. (2012). Defining the Nature of Thermal Intermediate in 3 State Folding Proteins: Apoflavodoxin, a Study Case. PLoS Comput Biol,  vol.8(8): e1002647
NO This work was supported by the Spanish Ministry of Science and Innovation (BIO2009-10964, BFU2010-16296 and Consolider E-Science), DGA-B89-2011, Instituto Nacional de Bioinformática, Scalalife EU-Grant and Fundación Marcelino Botín. RGF also thanks the Spanish Ministry of Science and Innovation for her postdoctoral fellowship and Juan de la Cierva contract
DS Minerva
RD 23 abr 2026