Peptide conformational preferences in osmolyte solutions: transfer free energies of decaalanine.
The nature in which the protecting osmolyte trimethylamine N-oxide (TMAO) and the denaturing osmolyte urea affect protein stability is investigated, simulating a decaalanine peptide model in multiple conformations of the denatured ensemble. Binary solutions of both osmolytes and mixed osmolyte solutions at physiologically relevant concentrations of 2:1 (urea:TMAO) are studied using standard molecular dynamics simulations and solvation free energy calculations. Component analysis reveals the differences in the importance of the van der Waals (vdW) and electrostatic interactions for protecting and denaturing osmolytes. We find that urea denaturation governed by transfer free energy differences is dominated by vdW attractions, whereas TMAO exerts its effect by causing unfavorable electrostatic interactions both in the binary solution and mixed osmolyte solution. Analysis of the results showed no evidence in the ternary solution of disruption of the correlations among the peptide and osmolytes, nor of significant changes in the strength of the water hydrogen bond network.
Department of Chemistry, University of Houston, Houston, Texas 77204-5003, United States.
Hironori
H
Kokubo
Char Y
CY
Hu
B Montgomery
BM
Pettitt
D000409:Alanine / Q000737:chemistry*; D008744:Methylamines / Q000494:pharmacology; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D009995:Osmosis / Q000187:drug effects; D011489:Protein Denaturation / Q000187:drug effects; D017433:Protein Structure, Secondary; D012996:Solutions; D013816:Thermodynamics; D014508:Urea / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D008744:Methylamines; D009842:Oligopeptides; D012996:Solutions; D014867:Water; D014508:Urea; C005855:trimethyloxamine; D000409:Alanine
Protein Sci. 2010 May;19(5):1011-22
20306490
J Phys Chem B. 2006 May 4;110(17):8885-92
16640449
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16928-33
18957546
J Am Chem Soc. 1965 Jun 5;87:2462-70
14330716
J Phys Chem B. 2006 Oct 26;110(42):21077-85
17048929
Proteins. 2010 Feb 15;78(3):695-704
19790265
Annu Rev Biochem. 2008;77:339-62
18518824
J Phys Chem B. 2009 Sep 24;113(38):12816-24
19708649
J Am Chem Soc. 2007 Dec 26;129(51):16126-31
18047342
J Am Chem Soc. 2002 Feb 20;124(7):1192-202
11841287
Biophys J. 2009 Nov 4;97(9):2559-66
19883599
Biophys J. 1998 May;74(5):2666-73
9591690
J Exp Biol. 2005 Aug;208(Pt 15):2819-30
16043587
J Phys Chem B. 2006 Jun 1;110(21):10514-8
16722761
Protein Sci. 2007 Feb;16(2):293-8
17189473
Biochemistry. 1992 Oct 20;31(41):9857-64
1390769
Structure. 1999 May;7(5):477-88
10378267
Proteins. 2008 Dec;73(4):802-13
18498104
J Phys Chem B. 2007 May 17;111(19):5233-42
17447807
J Phys Chem B. 2007 Jul 19;111(28):7932-3
17580863
Biochem J. 1979 Nov 1;183(2):317-23
534499
Biochemistry. 1994 Oct 25;33(42):12695-701
7918496
J Chem Phys. 2005 Apr 8;122(14):144107
15847516
Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15065-8
16214887
Biochemistry. 1997 Jul 29;36(30):9101-8
9230042
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16623-33
17075053
Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15317-22
17878304
J Biol Chem. 1981 Jul 25;256(14):7193-201
7251592
J Am Chem Soc. 2007 Apr 11;129(14):4476-82
17373796
J Chem Theory Comput. 2009 Oct 1;5(10):2583-2588
21857812
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2595-600
19196963
J Phys Chem B. 2005 Oct 13;109(40):19000-7
16853446
Nature. 2005 Sep 29;437(7059):640-7
16193038
Biochemistry. 1990 Feb 20;29(7):1924-31
2331472
J Comput Chem. 2003 Dec;24(16):1999-2012
14531054
Science. 1982 Sep 24;217(4566):1214-22
7112124
Protein Sci. 2003 Jul;12(7):1522-9
12824497