Development of a motif-based topology-independent structure comparison method to identify evolutionarily related folds.
Structure conservation, functional similarities, and homologous relationships that exist across diverse protein topologies suggest that some regions of the protein fold universe are continuous. However, the current structure classification systems are based on hierarchical organizations, which cannot accommodate structural relationships that span fold definitions. Here, we describe a novel, super-secondary-structure motif-based, topology-independent structure comparison method (SmotifCOMP) that is able to quantitatively identify structural relationships between disparate topologies. The basis of SmotifCOMP is a systematically defined super-secondary-structure motif library whose representative geometries are shown to be saturated in the Protein Data Bank and exhibit a unique distribution within the known folds. SmotifCOMP offers a robust and quantitative technique to compare domains that adopt different topologies since the method does not rely on a global superposition. SmotifCOMP is used to perform an exhaustive comparison of the known folds and the identified relationships are used to produce a nonhierarchical representation of the fold space that reflects the notion of a continuous and connected fold universe. The current work offers insight into previously hypothesized evolutionary relationships between disparate folds and provides a resource for exploring novel ones. Proteins 2016; 84:1859-1874. © 2016 Wiley Periodicals, Inc.
Department of Systems and Computational Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461.|Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461.
Joseph M
JM
Dybas
Department of Systems and Computational Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461.|Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, 10461.
Andras
A
Fiser
D000465:Algorithms; D020816:Amino Acid Motifs; D030562:Databases, Protein; D019143:Evolution, Molecular; D008958:Models, Molecular; D000072417:Protein Domains; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000145:classification; D040681:Structural Homology, Protein
D011506:Proteins
Smotif; fold evolution; structure classification; structure comparison; super-secondary structure motif
Curr Opin Struct Biol. 2008 Apr;18(2):170-7
18328690
Proteins. 2008 May 1;71(2):795-803
17979191
Structure. 2013 Jun 4;21(6):891-9
23685209
Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3733-8
24567391
Nature. 2012 Nov 8;491(7423):222-7
23135467
Acta Crystallogr A. 2005 Jul;61(Pt 4):478-80
15973002
J Mol Biol. 1995 Apr 7;247(4):536-40
7723011
Nat Struct Biol. 2001 Jan;8(1):5-7
11135656
Curr Opin Struct Biol. 2007 Jun;17(3):354-61
17580115
Bioinformatics. 2006 Jul 1;22(13):1658-9
16731699
Mol Biol Evol. 2010 Jun;27(6):1348-58
20106904
Nucleic Acids Res. 2001 Feb 1;29(3):638-43
11160884
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5441-6
18385384
Curr Opin Struct Biol. 2002 Jun;12(3):400-8
12127461
Methods Enzymol. 2003;374:492-509
14696386
Proc Natl Acad Sci U S A. 1999 May 25;96(11):6285-90
10339579
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W173-6
16844985
PLoS Comput Biol. 2009 Mar;5(3):e1000331
19325884
Curr Opin Struct Biol. 2006 Jun;16(3):399-408
16650981
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Nov 1;61(Pt 11):959-63
16511207
FEBS Lett. 2002 Jan 16;510(3):133-5
11801240
Nature. 2002 Apr 11;416(6881):657-60
11948354
Bioinformatics. 2005 Apr 15;21(8):1308-10
15604105
Curr Biol. 1999 Oct 21;9(20):1158-68
10531028
Curr Opin Struct Biol. 2009 Jun;19(3):329-34
19394812
Bioinformatics. 2005 Jun;21 Suppl 1:i449-58
15961490
Proteins. 2000 Feb 15;38(3):247-60
10713986
Protein Sci. 2003 Oct;12(10):2150-60
14500873
Nat Struct Biol. 2001 Jan;8(1):32-6
11135667
Structure. 2005 Jun;13(6):919-28
15939023
Nucleic Acids Res. 2000 Jan 1;28(1):235-42
10592235
Curr Opin Struct Biol. 1998 Jun;8(3):380-7
9666335
Expert Rev Proteomics. 2004 Jun;1(1):97-110
15966803
Structure. 2006 Oct;14(10):1489-98
17027498
J Struct Biol. 2001 May-Jun;134(2-3):167-85
11551177
Nucleic Acids Res. 2003 Jul 1;31(13):3370-4
12824330
Proc Natl Acad Sci U S A. 2014 Aug 12;111(32):11691-6
25071170
Protein Eng. 1999 Feb;12(2):85-94
10195279
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14056-61
16959887
Nature. 2002 Nov 14;420(6912):218-23
12432406
Proteins. 2007 May 15;67(3):559-68
17335003
Structure. 1999 Sep 15;7(9):1099-112
10508779
Nucleic Acids Res. 2003 Jul 1;31(13):3293-5
12824310
J Mol Biol. 2002 Aug 30;321(5):923-38
12206771
Curr Opin Struct Biol. 2009 Jun;19(3):321-8
19482467
EMBO J. 1986 Apr;5(4):823-6
3709526
Proc Natl Acad Sci U S A. 2009 Oct 13;106(41):17377-82
19805138
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3651-6
15705717
Methods Enzymol. 1996;266:635-43
8743710
Science. 2000 Sep 1;289(5484):1546-50
10968789
Genome Res. 2003 Nov;13(11):2498-504
14597658
J Mol Biol. 1989 Jul 5;208(1):1-22
2769748
Protein Eng. 1998 Sep;11(9):739-47
9796821
Science. 1996 Aug 2;273(5275):595-603
8662544
PLoS One. 2013 Oct 15;8(10):e77074
24143202
Nucleic Acids Res. 2013 Jan;41(Database issue):D490-8
23203873
Curr Opin Struct Biol. 2006 Jun;16(3):393-8
16678402
J Struct Biol. 2010 Dec;172(3):244-52
20691788
PLoS Comput Biol. 2015 Sep 15;11(9):e1004466
26372166
Biochemistry. 2006 Sep 5;45(35):10542-53
16939206
Structure. 2009 Aug 12;17(8):1051-62
19679085
Structure. 2005 Aug;13(8):1213-24
16084393
Biopolymers. 1983 Dec;22(12):2577-637
6667333
PLoS Comput Biol. 2010 Apr 22;6(4):e1000750
20421995
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3481-6
20133727
Bioinformatics. 2014 Jul 1;30(13):1935-6
24603983
Fold Des. 1997;2(3):S19-24
9218962
Nucleic Acids Res. 2008 Jan;36(Database issue):D419-25
18000004
J Mol Biol. 1981 Mar 25;147(1):195-7
7265238
BMC Struct Biol. 2009 Apr 17;9:23
19374763
Protein Sci. 2010 Jan;19(1):124-30
19937658
Structure. 1997 Aug 15;5(8):1093-108
9309224
Structure. 2004 Apr;12(4):569-81
15062080
PLoS Comput Biol. 2014 Dec 04;10(12):e1003926
25474468
Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12301-6
21737750
Nucleic Acids Res. 2006 Apr 14;34(7):2085-97
16617149
Nucleic Acids Res. 2014 Jan;42(Database issue):D310-4
24293656
Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2386-90
12606708
J Mol Biol. 1993 Sep 5;233(1):123-38
8377180
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2343-8
18227506
Nat Chem Biol. 2014 Sep;10(9):710-5
25038785
J Mol Biol. 2002 Nov 8;323(5):909-26
12417203
J Struct Biol. 2001 May-Jun;134(2-3):191-203
11551179