Alpha-helical topology prediction and generation of distance restraints in membrane proteins.
The field of protein structure prediction has seen significant advances in recent years. Researchers have followed a multitude of approaches, including methods based on comparative modeling, fold recognition and threading, and first-principles techniques. It is noteworthy that the structure prediction of membrane proteins is comparatively less studied by researchers in the field. A membrane protein is characterized by a protein structure that extends into or through the lipid-lipid bilayer of a cell. The structure is influenced by the combination of the hydrophobic bilayer region, the direct interaction with the bilayer, and the aqueous external environment. Due to the difficulty in obtaining reliable experimental structures, accurate computational prediction of membrane proteins is of paramount importance. An optimization model has been developed to predict the interhelical interactions in alpha-helical membrane proteins. A database of alpha-helical membrane proteins of known structure and limited sequence identity can be constructed to develop interaction probabilities. By then maximizing the occurrence of highly probable pairwise or three-residue interactions, realistic contacts can be predicted by imposing a number of geometrical constraints. The development of these low distance contacts can provide additional distance restraints for first principles-based approaches to the tertiary structure prediction problem. The proposed approach is shown to successfully predict interhelical contacts in several membrane protein systems, including bovine rhodopsin and the recently released human beta2 adrenergic receptor protein structure.
McAllister
Scott R
SR
Department of Chemical Engineering, Princeton University, Princeton, New Jersey, USA.
Floudas
Christodoulos A
CA
D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011336:Probability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins
In Silico Biol. 2002;2(1):19-33
11808871
Bioinformatics. 2001 Jul;17(7):646-53
11448883
Protein Sci. 2003 Aug;12(8):1750-61
12876324
J Mol Biol. 2002 Aug 9;321(2):363-78
12144792
Protein Sci. 2004 Jul;13(7):1908-17
15215532
Nat Struct Biol. 2000 Feb;7(2):154-60
10655619
Biophys J. 2003 Mar;84(3):1902-8
12609892
Biophys J. 2004 Dec;87(6):4075-86
15465852
Nature. 2007 Nov 15;450(7168):383-7
17952055
PLoS Comput Biol. 2006 Feb;2(2):e13
16485037
J Mol Biol. 2001 Aug 24;311(4):891-907
11518538
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
10592235
Proteins. 2006 Dec 1;65(4):930-52
17029234
Biochim Biophys Acta. 1998 Dec 8;1429(1):113-28
9920390
Proteins. 2004 Oct 1;57(1):51-86
15326594
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12622-7
12351677
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16123-8
17060607
Biochemistry. 1990 May 1;29(17):4031-7
1694455
Biophys J. 2002 May;82(5):2720-36
11964258
Science. 2000 Aug 4;289(5480):739-45
10926528
Science. 2007 Nov 23;318(5854):1258-65
17962520
Nature. 2002 Oct 3;419(6906):484-7
12368857
Annu Rev Biophys Biomol Struct. 1999;28:319-65
10410805
Curr Opin Drug Discov Devel. 2003 May;6(3):353-61
12833668
J Mol Biol. 2004 Nov 5;343(5):1409-38
15491621
Proteins. 2008 Feb 15;70(3):984-99
17847096
Comput Biol Chem. 2004 Oct;28(4):265-74
15548453
Comput Biol Chem. 2004 Feb;28(1):51-60
15022642
J Mol Biol. 1997 Oct 10;272(5):780-9
9368657
J Mol Biol. 2004 Sep 10;342(2):571-83
15327956
Protein Sci. 2001 Feb;10(2):455-8
11266632
Biochemistry. 1994 Mar 15;33(10):3038-49
8130217
J Mol Biol. 2001 Jan 19;305(3):567-80
11152613
Nat Rev Drug Discov. 2002 Sep;1(9):727-30
12209152
J Mol Biol. 2003 Mar 14;327(1):251-72
12614623
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5796-801
10823938
Nat Struct Biol. 2000 Feb;7(2):161-6
10655620
Protein Sci. 1998 Apr;7(4):1029-38
9568909
Bioinformatics. 2003 Aug 12;19(12):1589-91
12912846
J Mol Biol. 2003 Jun 13;329(4):831-40
12787681
Protein Sci. 2004 Oct;13(10):2613-27
15340162
J Comput Chem. 2004 Apr 15;25(5):632-6
14978706
Biochemistry. 1991 Apr 30;30(17):4237-44
2021617