Water molecules and hydrogen-bonded networks in bacteriorhodopsin--molecular dynamics simulations of the ground state and the M-intermediate.
Protein crystallography provides the structure of a protein, averaged over all elementary cells during data collection time. Thus, it has only a limited access to diffusive processes. This article demonstrates how molecular dynamics simulations can elucidate structure-function relationships in bacteriorhodopsin (bR) involving water molecules. The spatial distribution of water molecules and their corresponding hydrogen-bonded networks inside bR in its ground state (G) and late M intermediate conformations were investigated by molecular dynamics simulations. The simulations reveal a much higher average number of internal water molecules per monomer (28 in the G and 36 in the M) than observed in crystal structures (18 and 22, respectively). We found nine water molecules trapped and 19 diffusive inside the G-monomer, and 13 trapped and 23 diffusive inside the M-monomer. The exchange of a set of diffusive internal water molecules follows an exponential decay with a 1/e time in the order of 340 ps for the G state and 460 ps for the M state. The average residence time of a diffusive water molecule inside the protein is approximately 95 ps for the G state and 110 ps for the M state. We have used the Grotthuss model to describe the possible proton transport through the hydrogen-bonded networks inside the protein, which is built up in the picosecond-to-nanosecond time domains. Comparing the water distribution and hydrogen-bonded networks of the two different states, we suggest possible pathways for proton hopping and water movement inside bR.
Grudinin
Sergei
S
Institute for Structural Biology (IBI-2), Forschungszentrum Jülich, Jülich, Germany.
Büldt
Georg
G
Gordeliy
Valentin
V
Baumgaertner
Artur
A
D001436:Bacteriorhodopsins / Q000737:chemistry*; D001692:Biological Transport; D001703:Biophysics / Q000379:methods*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004058:Diffusion; D019281:Dimerization; D006217:Halobacterium / Q000378:metabolism; D006860:Hydrogen Bonding; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D010713:Phosphatidylcholines / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011522:Protons; D012984:Software; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D010713:Phosphatidylcholines; D011522:Protons; D014867:Water; D001436:Bacteriorhodopsins; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
Protein Sci. 1999 Feb;8(2):447-59
10048341
Nat Struct Biol. 1999 Mar;6(3):253-60
10074944
Annu Rev Biophys Biomol Struct. 1999;28:367-99
10410806
J Mol Biol. 1999 Aug 27;291(4):899-911
10452895
Science. 1999 Oct 8;286(5438):255-61
10514362
Biophys J. 2000 Feb;78(2):683-93
10653781
Proteins. 2000 Feb 15;38(3):261-72
10713987
Biophys J. 2000 Apr;78(4):1714-24
10733954
Biochim Biophys Acta. 2000 May 12;1458(1):135-47
10812029
Nature. 2000 Aug 10;406(6796):649-53
10949308
Nature. 2000 Aug 10;406(6796):653-7
10949309
Biophys Chem. 2000 Jul 15;85(2-3):229-48
10961509
Biochim Biophys Acta. 2000 Aug 30;1460(1):106-18
10984594
Biochim Biophys Acta. 2000 Aug 30;1460(1):133-56
10984596
Biochim Biophys Acta. 2000 Aug 30;1460(1):177-91
10984599
Biochim Biophys Acta. 2000 Aug 30;1460(1):192-203
10984600
Biophys Chem. 2000 Aug 30;86(2-3):249-57
11026689
Biophys J. 2000 Dec;79(6):2966-74
11106604
Biophys J. 2001 Apr;80(4):1691-702
11259283
J Mol Biol. 2001 Aug 17;311(3):605-21
11493013
Biochemistry (Mosc). 2001 Nov;66(11):1192-6
11743864
Biophys J. 2002 May;82(5):2304-16
11964221
Proteins. 2002 Jun 1;47(4):534-45
12001232
Biophys J. 2002 Sep;83(3):1281-97
12202355
Biochemistry. 2003 Aug 26;42(33):9875-88
12924936
J Mol Biol. 1992 Mar 20;224(2):473-86
1313886
J Mol Biol. 2003 Oct 3;332(5):1183-93
14499620
J Mol Biol. 2004 Jan 9;335(2):531-46
14672661
Biophys J. 2004 Feb;86(2):705-17
14747309
Annu Rev Physiol. 2004;66:665-88
14977418
Biophys J. 2004 Apr;86(4):1873-89
15041635
Science. 1991 Nov 15;254(5034):974-80
1948083
J Mol Biol. 1990 Jul 5;214(1):15-9
2164582
Proc Natl Acad Sci U S A. 1989 Jul;86(13):4943-7
2544884
J Am Chem Soc. 1988 Mar 1;110(6):1657-66
27557051
J Comput Chem. 1986 Apr;7(2):230-252
29160584
J Mol Biol. 1995 Feb 3;245(5):682-97
7531248
J Mol Biol. 1995 Feb 3;245(5):698-709
7531249
J Biol Chem. 1995 Nov 10;270(45):27122-6
7592966
J Mol Biol. 1995 Jun 30;250(1):94-111
7602600
Biophys J. 1995 Apr;68(4):1270-82
7787017
Science. 1995 Mar 24;267(5205):1813-7
7892604
Structure. 1993 Dec 15;1(4):223-6
8081736
Biophys J. 1995 Dec;69(6):2745-60
8599681
Biophys J. 1996 Aug;71(2):670-81
8842206
Biophys J. 1996 Sep;71(3):1172-8
8873991
Biopolymers. 1996 Mar;38(3):305-20
8906967
Faraday Discuss. 1996;(103):227-44
9136639
Biochemistry. 1997 Jul 22;36(29):8671-6
9289012
J Mol Biol. 1998 Jan 30;275(4):625-34
9466936
Biochemistry. 1998 Feb 24;37(8):2496-506
9485398
Biophys J. 1998 Jul;75(1):33-40
9649365
Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):103-8
9874779