Interpretation of 2H-NMR experiments on the orientation of the transmembrane helix WALP23 by computer simulations.
Orientation, dynamics, and packing of transmembrane helical peptides are important determinants of membrane protein structure, dynamics, and function. Because it is difficult to investigate these aspects by studying real membrane proteins, model transmembrane helical peptides are widely used. NMR experiments provide information on both orientation and dynamics of peptides, but they require that motional models be interpreted. Different motional models yield different interpretations of quadrupolar splittings (QS) in terms of helix orientation and dynamics. Here, we use coarse-grained (CG) molecular dynamics (MD) simulations to investigate the behavior of a well-known model transmembrane peptide, WALP23, under different hydrophobic matching/mismatching conditions. We compare experimental (2)H-NMR QS (directly measured in experiments), as well as helix tilt angle and azimuthal rotation (not directly measured), with CG MD simulation results. For QS, the agreement is significantly better than previously obtained with atomistic simulations, indicating that equilibrium sampling is more important than atomistic details for reproducing experimental QS. Calculations of helix orientation confirm that the interpretation of QS depends on the motional model used. Our simulations suggest that WALP23 can form dimers, which are more stable in an antiparallel arrangement. The origin of the preference for the antiparallel orientation lies not only in electrostatic interactions but also in better surface complementarity. In most cases, a mixture of monomers and antiparallel dimers provides better agreement with NMR data compared to the monomer and the parallel dimer. CG MD simulations allow predictions of helix orientation and dynamics and interpretation of QS data without requiring any assumption about the motional model.
Monticelli
Luca
L
INSERM UMR-S 665, DSIMB, Paris, France.
Tieleman
D Peter
DP
Fuchs
Patrick F J
PF
D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D012399:Rotation; D013997:Time Factors; D014364:Tryptophan
D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D014364:Tryptophan
J Chem Theory Comput. 2008 May;4(5):819-34
26621095
Curr Opin Struct Biol. 2000 Oct;10(5):593-600
11042459
J Mol Biol. 1997 Oct 10;272(5):780-9
9368657
Chem Phys Lipids. 2005 Jun;135(2):223-44
15921980
Biophys J. 2009 Apr 22;96(8):3223-32
19383466
Biophys J. 2004 Jun;86(6):3709-21
15189867
J Phys Chem B. 2007 Jul 12;111(27):7812-24
17569554
Biochemistry. 2002 Mar 5;41(9):3073-80
11863446
Biophys J. 2006 Apr 1;90(7):2326-43
16428278
Biophys J. 2004 Dec;87(6):4075-86
15465852
Biophys J. 2007 Dec 15;93(12):4278-88
17720729
Biophys J. 2010 May 19;98(9):1864-72
20441750
Biochemistry. 2003 May 13;42(18):5341-8
12731875
Biochemistry. 2001 Apr 24;40(16):5000-10
11305916
Bioelectrochemistry. 2002 May 15;56(1-2):135-40
12009460
J Am Chem Soc. 2007 Dec 12;129(49):15174-81
18001020
Biochim Biophys Acta. 2004 Nov 3;1666(1-2):62-87
15519309
Biochemistry. 2007 Feb 13;46(6):1457-65
17279611
J Comput Chem. 2009 Aug;30(11):1622-33
19496166
Proc Natl Acad Sci U S A. 2006 Sep 12;103(37):13658-63
16954199
Biophys J. 2005 Mar;88(3):1778-98
15738466
Biophys J. 2009 Apr 22;96(8):3233-41
19383467
Eur Biophys J. 2010 Mar;39(4):609-21
20020122
Mol Membr Biol. 2003 Oct-Dec;20(4):271-84
14578043
FEBS Lett. 1999 Sep 24;458(3):271-7
10570923
Biochemistry. 2005 Jan 11;44(1):2-10
15628840
Biophys J. 1984 Aug;46(2):141-53
6478029
J Biomol NMR. 2003 Aug;26(4):283-95
12815256
Biochemistry. 2005 Jan 25;44(3):1004-12
15654757
Proc Natl Acad Sci U S A. 2005 May 10;102(19):6771-6
15860587
Biochim Biophys Acta. 2004 Nov 3;1666(1-2):2-18
15519305
J Struct Biol. 2003 Apr;142(1):144-53
12718926
J Am Chem Soc. 2008 Sep 24;130(38):12584-5
18763771
Structure. 2008 May;16(5):787-97
18462683
Biochim Biophys Acta. 1998 Nov 10;1376(3):401-15
9805000
Biophys J. 2009 Oct 21;97(8):2258-66
19843458
Curr Opin Struct Biol. 2001 Oct;11(5):540-7
11785753
Biochemistry. 2009 Dec 8;48(48):11441-8
19860438
Biophys J. 2009 May 6;96(9):3648-62
19413970
J Mol Biol. 1997 Sep 12;272(1):106-20
9299341
Biochim Biophys Acta. 1998 Nov 10;1376(3):339-52
9804985
Biophys J. 2005 Jan;88(1):105-17
15489306
Biophys J. 2002 Sep;83(3):1479-88
12202373
J Biol Chem. 2005 Nov 25;280(47):39324-31
16169846
J Phys Chem B. 2009 Sep 10;113(36):12257-64
19689145
FEBS Lett. 2003 Nov 27;555(1):134-8
14630333
Chem Phys Lipids. 2006 Jun;141(1-2):2-29
16620797
Methods. 2007 Apr;41(4):475-88
17367719