TY - JOUR
T1 - Osmolyte effects on protein stability and solubility
T2 - A balancing act between backbone and side-chains
AU - Auton, Matthew
AU - Rösgen, Jörg
AU - Sinev, Mikhail
AU - Holthauzen, Luis Marcelo F.
AU - Bolen, D. Wayne
N1 - Funding Information:
We dedicate this paper to the memory of Prof. Stanley J. Gill, one of the original founders of the Gibbs Conference. His contributions and belief in the Conference were instrumental in launching and sustaining the meeting in its early years. The authors gratefully acknowledge support by NIH through grant GM049760 to JR, and by DoD through DURIP grant W911NF-06-1-0131 to UTMB.
PY - 2011/11
Y1 - 2011/11
N2 - In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We've addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (ΔG tr, N) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein's solvent exposed side chain and backbone component parts. ΔG tr, D is predicted using a self avoiding random coil model for the protein, and ΔG tr, D - ΔG tr, N, predicts the m-value, a quantity that measures the osmolyte effect on the N D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12 kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles.
AB - In adaptation biology the discovery of intracellular osmolyte molecules that in some cases reach molar levels, raises questions of how they influence protein thermodynamics. We've addressed such questions using the premise that from atomic coordinates, the transfer free energy of a native protein (ΔG tr, N) can be predicted by summing measured water-to-osmolyte transfer free energies of the protein's solvent exposed side chain and backbone component parts. ΔG tr, D is predicted using a self avoiding random coil model for the protein, and ΔG tr, D - ΔG tr, N, predicts the m-value, a quantity that measures the osmolyte effect on the N D transition. Using literature and newly measured m-values we show 1:1 correspondence between predicted and measured m-values covering a range of 12 kcal/mol/M in protein stability for 46 proteins and 9 different osmolytes. Osmolytes present a range of side chain and backbone effects on N and D solubility and protein stability key to their biological roles.
KW - Folding
KW - Osmolyte
KW - Protein stability
KW - Solubility
KW - Urea
KW - m-Value
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U2 - 10.1016/j.bpc.2011.05.012
DO - 10.1016/j.bpc.2011.05.012
M3 - Article
C2 - 21683504
AN - SCOPUS:80052319202
SN - 0301-4622
VL - 159
SP - 90
EP - 99
JO - Biophysical Chemistry
JF - Biophysical Chemistry
IS - 1
ER -