defining the nature of thermal intermediate in 3 state folding proteins apoflavodoxin, a study case热的本质定义中间折叠蛋白质apoflavodoxin 3状态,一个研究案例.pdfVIP

Defining the Nature of Thermal Intermediate in 3 State Folding Proteins: Apoflavodoxin, a Study Case ´ ˜ 1,2 ´ 3 4,5 4,5 1,6 Rebeca Garcıa-Fandino , Pau Bernado , Sara Ayuso-Tejedor , Javier Sancho , Modesto Orozco * 1Joint IRB BSC Program in Computational Biology, Institute for Research in Biomedicine, Barcelona, Spain, 2 Department of Organic Chemistry and Center for Research in Biological Chemistry and Molecular Materials, Santiago de Compostela University, Santiago de Compostela, Spain, 3 Centre de Biochimie Structurale, INSERM U1054, CNRS ´ ´ ´ UMR 5048, Universite Montpellier 1 and 2, Montpellier, France, 4 Departamento de Bioquımica y Biologıa Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain, 5 Joint Unit BIFI-IQFR, CSIC, Spain, Biocomputation and Physics of Complex Systems Institute (BIFI), Universidad de Zaragoza, Zaragoza, Spain, ´ 6 Departament de Bioquımica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain Abstract 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-loo