TY - JOUR
T1 - Denatured state is critical in determining the properties of model proteins designed on different folds
AU - Amatori, Andrea
AU - Ferkinghoff-Borg, Jesper
AU - Tiana, Guido
AU - Broglia, Richardo A.
PY - 2008
Y1 - 2008
N2 - The thermodynamics of proteins designed on three common folds (SH3, chymotrypsin inhibitor 2 [CI2], and protein G) is studied with a simplified C alpha, model and compared with the thermodynamics of proteins designed on random-generated folds. The model allows to design sequences to fold within a dRMSD ranging from 1.2 to 4.2 angstrom from the crystallographic native conformation and to study properties that are hard to be measured experimentally. It is found that the denatured state of all of them is not random but is, to different extents, partially structured. The degree of structure is more abundant for SH3 and protein G, giving rise to a weaker stability but a more efficient folding kinetics than CI2 and, even more, than the random-generated folds. Consequently, the features of the unfolded state seem to be as important in the determination of the thermodynamic properties of these proteins as the features of the native state.
AB - The thermodynamics of proteins designed on three common folds (SH3, chymotrypsin inhibitor 2 [CI2], and protein G) is studied with a simplified C alpha, model and compared with the thermodynamics of proteins designed on random-generated folds. The model allows to design sequences to fold within a dRMSD ranging from 1.2 to 4.2 angstrom from the crystallographic native conformation and to study properties that are hard to be measured experimentally. It is found that the denatured state of all of them is not random but is, to different extents, partially structured. The degree of structure is more abundant for SH3 and protein G, giving rise to a weaker stability but a more efficient folding kinetics than CI2 and, even more, than the random-generated folds. Consequently, the features of the unfolded state seem to be as important in the determination of the thermodynamic properties of these proteins as the features of the native state.
U2 - 10.1002/prot.21599
DO - 10.1002/prot.21599
M3 - Journal article
SN - 0887-3585
VL - 70
SP - 1047
EP - 1055
JO - Proteins - Structure Function and Bioinformatics
JF - Proteins - Structure Function and Bioinformatics
IS - 3
ER -