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A simple simulation model can reproduce the thermodynamic folding intermediate of apoflavodoxin
Author(s) -
Larriva María,
Prieto Lidia,
Bruscolini Pierpaolo,
Rey Antonio
Publication year - 2010
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22521
Subject(s) - protein folding , folding (dsp implementation) , native state , downhill folding , topology (electrical circuits) , lattice protein , intermediate state , phi value analysis , contact order , population , crystallography , physics , chemistry , chemical physics , mathematics , combinatorics , atomic physics , nuclear magnetic resonance , demography , sociology , electrical engineering , engineering
Flavodoxins are single domain proteins with an α/ β structure, whose function and folding have been well studied. Detailed experiments have shown that several members of this protein family present a stable intermediate, which accumulates along the folding process. In this work, we use a coarse‐grained model for protein folding, whose interactions are based on the topology of the native state, to analyze the thermodynamic characteristics of the folding of Anabaena apoflavodoxin. Our model shows evidence for the existence of a thermodynamic folding intermediate, which reaches a significant population along the thermal transition. According to our simulation results, the intermediate is compact, well packed, and involves distortions of the native structure similar to those experimentally found. These mainly affect the long loop in the protein surface comprising residues 120–139. Although the agreement between simulation and experiment is not perfect, something impossible for a crude model, our results show that the topology of the native state is able to dictate a folding process which includes the presence of an intermediate for this protein. Proteins 2010. © 2009 Wiley‐Liss, Inc.