Integration of Diverse Research Methods to Analyze and Engineer Ca-Binding Proteins: From Prediction to Production.
In recent years, increasingly sophisticated computational and bioinformatics tools have evolved for the analyses of protein structure, function, ligand interactions, modeling and energetics. This includes the development of algorithms to recursively evaluate side-chain rotamer permutations, identify regions in a 3D structure that meet some set of search parameters, calculate and minimize energy values, and provide high-resolution visual tools for theoretical modeling. Here we discuss the interdependency between different areas of bioinformatics, the evolution of different algorithm design approaches, and finally the transition from theoretical models to real-world design and application as they relate to Ca(2+)-binding proteins. Within this context, it has become evident that significant pre-experimental design and calculations can be modeled through computational methods, thus eliminating potentially unproductive research and increasing our confidence in the correlation between real and theoretical models. Moving from prediction to production, it is anticipated that bioinformatics tools will play an increasingly significant role in research and development, improving our ability to both understand the physiological roles of Ca(2+) and other metals and to extend that knowledge to the design of function-specific synthetic proteins capable of fulfilling different roles in medical diagnostics and therapeutics.
Kirberger
Michael
M
Department of Chemistry, Center for Drug Design and Biotechnology, Georgia State University, Atlanta, GA 30303, USA.
Wang
Xue
X
Zhao
Kun
K
Tang
Shen
S
Chen
Guantao
G
Yang
Jenny J
JJ
J Am Chem Soc. 2005 Mar 23;127(11):3743-50
15771508
Biochemistry. 1990 May 1;29(17):4188-93
2193686
Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10147-52
16006526
J Struct Funct Genomics. 2002;2(3):135-43
12836704
Protein Eng. 1999 Feb;12(2):129-39
10195284
J Biol Chem. 1973 May 10;248(9):3313-26
4700463
Biochemistry. 2007 Oct 30;46(43):12275-88
17924653
EMBO J. 1996 Nov 1;15(21):5824-32
8918460
J Biol Chem. 1986 Feb 25;261(6):2638-44
3949740
Protein Sci. 1997 Aug;6(8):1661-81
9260279
Q Rev Biophys. 1994 Aug;27(3):219-90
7899550
J Biol Inorg Chem. 2001 Jun;6(5-6):479-89
11472012
Protein Eng. 2001 Dec;14(12):1001-13
11809931
Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):857-67
10930832
J Mol Biol. 2004 Oct 29;343(4):971-84
15476814
Biochemistry. 1991 Jan 8;30(1):97-106
1899021
Biochemistry. 1989 Jul 11;28(14):6081-5
2775752
Annu Rev Biophys Biomol Struct. 2000;29:291-325
10940251
Chem Rev. 2003 Mar;103(3):773-88
12630852
J Am Chem Soc. 2004 May 19;126(19):5990-8
15137763
Bioinformatics. 2000 Apr;16(4):404-5
10869041
Protein Sci. 2008 Mar;17(3):439-49
18287277
Biochemistry. 1999 Jan 5;38(1):2-10
9890877
Proteins. 2006 Nov 15;65(3):643-55
16981205
J Am Chem Soc. 2008 Jul 23;130(29):9260-7
18576649
Bioinformatics. 1998;14(10):892-3
9927721
J Am Chem Soc. 2003 May 21;125(20):6165-71
12785848
J Biol Chem. 2007 Jun 29;282(26):19000-10
17478419
Acta Crystallogr D Biol Crystallogr. 2006 Jun;62(Pt 6):678-82
16699196
Acta Crystallogr D Biol Crystallogr. 1999 Aug;55(Pt 8):1432-43
10417412
Protein Eng. 1990 Oct;4(1):57-63
2290835
Nat Struct Biol. 1995 Sep;2(9):758-67
7552747
J Mol Biol. 2007 Jan 5;365(1):257-73
17059826
Biochemistry. 2009 Jan 20;48(2):388-98
19102677
Nature. 1990 Sep 6;347(6288):44-9
2395461
Proteins. 2000 May 15;39(3):261-8
10737948
Proteins. 2002 May 15;47(3):344-56
11948788
Structure. 2006 Feb;14(2):265-74
16472746
Biometals. 1998 Dec;11(4):297-318
10191495
Proteins. 2006 Jul 1;64(1):34-42
16617426
J Mol Biol. 2000 Dec 15;304(5):967-82
11124040
J Biol Chem. 2000 Nov 24;275(47):37021-9
10896943
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5648-52
2377604
J Biol Inorg Chem. 2008 Sep;13(7):1169-81
18594878
BMC Bioinformatics. 2006 Dec 18;7 Suppl 5:S13
17254297
Nucleic Acids Res. 2003 Jul 1;31(13):3381-5
12824332
Biochimie. 1985 May;67(5):555-60
3839696
J Mol Biol. 1997 Apr 18;267(5):1268-82
9150411
Biochemistry. 2006 May 9;45(18):5848-56
16669627
Adv Protein Chem. 1991;42:1-76
1793004
Acta Crystallogr D Biol Crystallogr. 2001 Mar;57(Pt 3):401-11
11223517
J Am Chem Soc. 2003 Aug 6;125(31):9318-28
12889961
J Mol Biol. 2005 Apr 1;347(3):483-7
15755444
Protein Sci. 2004 Oct;13(10):2665-72
15340165
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):817-21
8290605
Pac Symp Biocomput. 2008;:332-43
18229697
J Virol. 2007 Jul;81(14):7517-28
17475644
J Biol Chem. 1989 Dec 5;264(34):20817-21
2684986
Protein Eng Des Sel. 2008 Feb;21(2):115-20
18283055
J Mol Biol. 2001 Feb 2;305(5):1011-24
11162110
Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13968-73
16966599
J Mol Biol. 2004 Sep 3;342(1):307-20
15313626
Nat Cell Biol. 2000 Jul;2(7):392-8
10878803
Acc Chem Res. 2007 Jan;40(1):85-93
17226948
Proteins. 2001 May 15;43(3):271-9
11288177
Biochemistry. 1997 Aug 12;36(32):9917-26
9245425
Protein Eng. 1990 Oct;4(1):49-56
2290834
Protein Eng. 1991 Jun;4(5):531-7
1891460
Adv Protein Chem. 1991;42:77-144
1793008
J Am Chem Soc. 2005 Feb 23;127(7):2085-93
15713084
Protein Profile. 1995;2(4):297-490
7553064
Proteins. 2003 Feb 1;50(2):272-82
12486721
Biochem Cell Biol. 1990 Mar;68(3):587-601
2198059
J Mol Biol. 2007 Jul 27;370(5):887-98
17553524
Protein Sci. 1995 Apr;4(4):622-35
7613462
FEBS J. 2008 Oct;275(20):5048-61
18785925
J Mol Biol. 1991 Dec 5;222(3):763-85
1749000
Blood. 1990 Jul 1;76(1):1-16
2194585
Biochemistry. 1988 May 31;27(11):4198-206
3415981
J Inorg Biochem. 2005 Jun;99(6):1376-83
15917089
Nat Struct Biol. 1994 May;1(5):334-40
7664040
Nat Struct Biol. 1995 Sep;2(9):768-76
7552748
Int J Neural Syst. 2005 Feb-Apr;15(1-2):71-84
15912584
Proteins. 2005 May 1;59(2):221-30
15726624
Science. 1997 Oct 3;278(5335):82-7
9311930
Protein Sci. 2000 Jan;9(1):73-82
10739249
Nucleic Acids Res. 2003 Jul 1;31(13):3692-7
12824396
Protein Sci. 1998 Feb;7(2):270-82
9521102
Biochemistry. 1996 May 28;35(21):6697-705
8639620
J Am Chem Soc. 2003 Mar 12;125(10):3168-80
12617685
Methods Mol Biol. 2000;132:47-69
10547831
Proteins. 2008 Jan 1;70(1):208-17
17657805
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W321-6
15215403
Biochemistry. 1991 Sep 3;30(35):8690-7
1653605
Annu Rev Biochem. 1989;58:951-98
2673026
Protein Eng. 2002 Jul;15(7):571-4
12200539
Proteins. 2009 Jun;75(4):787-98
19003991
J Biol Chem. 1989 Oct 5;264(28):16620-8
2777802
J Biol Chem. 1991 May 5;266(13):8050-4
1902469
Pac Symp Biocomput. 1998;:497-508
9697207