TY - JOUR
T1 - Stability of proteins
T2 - Temperature, pressure and the role of the solvent
AU - Scharnagl, Christina
AU - Reif, Maria
AU - Friedrich, Josef
N1 - Funding Information:
We acknowledge financial support from the DFG (Fr 456/25-4, A1 and SFB 533, B5 and C2) and from the Fonds der Chemischen Industrie. We want to thank our friends Jane Vanderkooi, Wolfgang Doster and Harald Lesch who have contributed a lot to this work through stimulating discussions and through experimental support.
PY - 2005/6/1
Y1 - 2005/6/1
N2 - We focus on the various aspects of the physics related to the stability of proteins. We review the pure thermodynamic aspects of the response of a protein to pressure and temperature variations and discuss the respective stability phase diagram. We relate the experimentally observed shape of this diagram to the low degree of correlation between the fluctuations of enthalpy and volume changes associated with the folding-denaturing transition and draw attention to the fact that one order parameter is not enough to characterize the transition. We discuss in detail microscopic aspects of the various contributions to the free energy gap of proteins and put emphasis on how a cosolvent may either enlarge or diminish this gap. We review briefly the various experimental approaches to measure changes in protein stability induced by cosolvents, denaturants, but also by pressure and temperature. Finally, we discuss in detail our own molecular dynamics simulations on cytochrome c and show what happens under high pressure, how glycerol influences structure and volume fluctuations, and how all this compares with experiments.
AB - We focus on the various aspects of the physics related to the stability of proteins. We review the pure thermodynamic aspects of the response of a protein to pressure and temperature variations and discuss the respective stability phase diagram. We relate the experimentally observed shape of this diagram to the low degree of correlation between the fluctuations of enthalpy and volume changes associated with the folding-denaturing transition and draw attention to the fact that one order parameter is not enough to characterize the transition. We discuss in detail microscopic aspects of the various contributions to the free energy gap of proteins and put emphasis on how a cosolvent may either enlarge or diminish this gap. We review briefly the various experimental approaches to measure changes in protein stability induced by cosolvents, denaturants, but also by pressure and temperature. Finally, we discuss in detail our own molecular dynamics simulations on cytochrome c and show what happens under high pressure, how glycerol influences structure and volume fluctuations, and how all this compares with experiments.
KW - Cosolvent and stability
KW - Fluctuation and correlation
KW - Folding-denaturing transition
KW - Molecular dynamics simulation
KW - Phase diagram of protein
KW - Protein-solvent interaction
KW - Thermodynamics of protein
UR - http://www.scopus.com/inward/record.url?scp=20144369761&partnerID=8YFLogxK
U2 - 10.1016/j.bbapap.2005.03.002
DO - 10.1016/j.bbapap.2005.03.002
M3 - Review article
C2 - 15893966
AN - SCOPUS:20144369761
SN - 1570-9639
VL - 1749
SP - 187
EP - 213
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 2
ER -