title: Integration of Diverse Research Methods to Analyze and Engineer Ca-Binding Proteins: From Prediction to Production.
abstract: 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.
authors.affiliation: Department of Chemistry, Center for Drug Design and Biotechnology, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kirberger
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.forename: Shen
authors.initials: S
authors.lastname: Tang
authors.forename: Guantao
authors.initials: G
authors.lastname: Chen
authors.forename: Jenny J
authors.initials: JJ
authors.lastname: Yang
references.citation: J Am Chem Soc. 2005 Mar 23;127(11):3743-50
references.pmid: 15771508
references.citation: Biochemistry. 1990 May 1;29(17):4188-93
references.pmid: 2193686
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10147-52
references.pmid: 16006526
references.citation: J Struct Funct Genomics. 2002;2(3):135-43
references.pmid: 12836704
references.citation: Protein Eng. 1999 Feb;12(2):129-39
references.pmid: 10195284
references.citation: J Biol Chem. 1973 May 10;248(9):3313-26
references.pmid: 4700463
references.citation: Biochemistry. 2007 Oct 30;46(43):12275-88
references.pmid: 17924653
references.citation: EMBO J. 1996 Nov 1;15(21):5824-32
references.pmid: 8918460
references.citation: J Biol Chem. 1986 Feb 25;261(6):2638-44
references.pmid: 3949740
references.citation: Protein Sci. 1997 Aug;6(8):1661-81
references.pmid: 9260279
references.citation: Q Rev Biophys. 1994 Aug;27(3):219-90
references.pmid: 7899550
references.citation: J Biol Inorg Chem. 2001 Jun;6(5-6):479-89
references.pmid: 11472012
references.citation: Protein Eng. 2001 Dec;14(12):1001-13
references.pmid: 11809931
references.citation: Acta Crystallogr D Biol Crystallogr. 2000 Jul;56(Pt 7):857-67
references.pmid: 10930832
references.citation: J Mol Biol. 2004 Oct 29;343(4):971-84
references.pmid: 15476814
references.citation: Biochemistry. 1991 Jan 8;30(1):97-106
references.pmid: 1899021
references.citation: Biochemistry. 1989 Jul 11;28(14):6081-5
references.pmid: 2775752
references.citation: Annu Rev Biophys Biomol Struct. 2000;29:291-325
references.pmid: 10940251
references.citation: Chem Rev. 2003 Mar;103(3):773-88
references.pmid: 12630852
references.citation: J Am Chem Soc. 2004 May 19;126(19):5990-8
references.pmid: 15137763
references.citation: Bioinformatics. 2000 Apr;16(4):404-5
references.pmid: 10869041
references.citation: Protein Sci. 2008 Mar;17(3):439-49
references.pmid: 18287277
references.citation: Biochemistry. 1999 Jan 5;38(1):2-10
references.pmid: 9890877
references.citation: Proteins. 2006 Nov 15;65(3):643-55
references.pmid: 16981205
references.citation: J Am Chem Soc. 2008 Jul 23;130(29):9260-7
references.pmid: 18576649
references.citation: Bioinformatics. 1998;14(10):892-3
references.pmid: 9927721
references.citation: J Am Chem Soc. 2003 May 21;125(20):6165-71
references.pmid: 12785848
references.citation: J Biol Chem. 2007 Jun 29;282(26):19000-10
references.pmid: 17478419
references.citation: Acta Crystallogr D Biol Crystallogr. 2006 Jun;62(Pt 6):678-82
references.pmid: 16699196
references.citation: Acta Crystallogr D Biol Crystallogr. 1999 Aug;55(Pt 8):1432-43
references.pmid: 10417412
references.citation: Protein Eng. 1990 Oct;4(1):57-63
references.pmid: 2290835
references.citation: Nat Struct Biol. 1995 Sep;2(9):758-67
references.pmid: 7552747
references.citation: J Mol Biol. 2007 Jan 5;365(1):257-73
references.pmid: 17059826
references.citation: Biochemistry. 2009 Jan 20;48(2):388-98
references.pmid: 19102677
references.citation: Nature. 1990 Sep 6;347(6288):44-9
references.pmid: 2395461
references.citation: Proteins. 2000 May 15;39(3):261-8
references.pmid: 10737948
references.citation: Proteins. 2002 May 15;47(3):344-56
references.pmid: 11948788
references.citation: Structure. 2006 Feb;14(2):265-74
references.pmid: 16472746
references.citation: Biometals. 1998 Dec;11(4):297-318
references.pmid: 10191495
references.citation: Proteins. 2006 Jul 1;64(1):34-42
references.pmid: 16617426
references.citation: J Mol Biol. 2000 Dec 15;304(5):967-82
references.pmid: 11124040
references.citation: J Biol Chem. 2000 Nov 24;275(47):37021-9
references.pmid: 10896943
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(15):5648-52
references.pmid: 2377604
references.citation: J Biol Inorg Chem. 2008 Sep;13(7):1169-81
references.pmid: 18594878
references.citation: BMC Bioinformatics. 2006 Dec 18;7 Suppl 5:S13
references.pmid: 17254297
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3381-5
references.pmid: 12824332
references.citation: Biochimie. 1985 May;67(5):555-60
references.pmid: 3839696
references.citation: J Mol Biol. 1997 Apr 18;267(5):1268-82
references.pmid: 9150411
references.citation: Biochemistry. 2006 May 9;45(18):5848-56
references.pmid: 16669627
references.citation: Adv Protein Chem. 1991;42:1-76
references.pmid: 1793004
references.citation: Acta Crystallogr D Biol Crystallogr. 2001 Mar;57(Pt 3):401-11
references.pmid: 11223517
references.citation: J Am Chem Soc. 2003 Aug 6;125(31):9318-28
references.pmid: 12889961
references.citation: J Mol Biol. 2005 Apr 1;347(3):483-7
references.pmid: 15755444
references.citation: Protein Sci. 2004 Oct;13(10):2665-72
references.pmid: 15340165
references.citation: Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):817-21
references.pmid: 8290605
references.citation: Pac Symp Biocomput. 2008;:332-43
references.pmid: 18229697
references.citation: J Virol. 2007 Jul;81(14):7517-28
references.pmid: 17475644
references.citation: J Biol Chem. 1989 Dec 5;264(34):20817-21
references.pmid: 2684986
references.citation: Protein Eng Des Sel. 2008 Feb;21(2):115-20
references.pmid: 18283055
references.citation: J Mol Biol. 2001 Feb 2;305(5):1011-24
references.pmid: 11162110
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13968-73
references.pmid: 16966599
references.citation: J Mol Biol. 2004 Sep 3;342(1):307-20
references.pmid: 15313626
references.citation: Nat Cell Biol. 2000 Jul;2(7):392-8
references.pmid: 10878803
references.citation: Acc Chem Res. 2007 Jan;40(1):85-93
references.pmid: 17226948
references.citation: Proteins. 2001 May 15;43(3):271-9
references.pmid: 11288177
references.citation: Biochemistry. 1997 Aug 12;36(32):9917-26
references.pmid: 9245425
references.citation: Protein Eng. 1990 Oct;4(1):49-56
references.pmid: 2290834
references.citation: Protein Eng. 1991 Jun;4(5):531-7
references.pmid: 1891460
references.citation: Adv Protein Chem. 1991;42:77-144
references.pmid: 1793008
references.citation: J Am Chem Soc. 2005 Feb 23;127(7):2085-93
references.pmid: 15713084
references.citation: Protein Profile. 1995;2(4):297-490
references.pmid: 7553064
references.citation: Proteins. 2003 Feb 1;50(2):272-82
references.pmid: 12486721
references.citation: Biochem Cell Biol. 1990 Mar;68(3):587-601
references.pmid: 2198059
references.citation: J Mol Biol. 2007 Jul 27;370(5):887-98
references.pmid: 17553524
references.citation: Protein Sci. 1995 Apr;4(4):622-35
references.pmid: 7613462
references.citation: FEBS J. 2008 Oct;275(20):5048-61
references.pmid: 18785925
references.citation: J Mol Biol. 1991 Dec 5;222(3):763-85
references.pmid: 1749000
references.citation: Blood. 1990 Jul 1;76(1):1-16
references.pmid: 2194585
references.citation: Biochemistry. 1988 May 31;27(11):4198-206
references.pmid: 3415981
references.citation: J Inorg Biochem. 2005 Jun;99(6):1376-83
references.pmid: 15917089
references.citation: Nat Struct Biol. 1994 May;1(5):334-40
references.pmid: 7664040
references.citation: Nat Struct Biol. 1995 Sep;2(9):768-76
references.pmid: 7552748
references.citation: Int J Neural Syst. 2005 Feb-Apr;15(1-2):71-84
references.pmid: 15912584
references.citation: Proteins. 2005 May 1;59(2):221-30
references.pmid: 15726624
references.citation: Science. 1997 Oct 3;278(5335):82-7
references.pmid: 9311930
references.citation: Protein Sci. 2000 Jan;9(1):73-82
references.pmid: 10739249
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3692-7
references.pmid: 12824396
references.citation: Protein Sci. 1998 Feb;7(2):270-82
references.pmid: 9521102
references.citation: Biochemistry. 1996 May 28;35(21):6697-705
references.pmid: 8639620
references.citation: J Am Chem Soc. 2003 Mar 12;125(10):3168-80
references.pmid: 12617685
references.citation: Methods Mol Biol. 2000;132:47-69
references.pmid: 10547831
references.citation: Proteins. 2008 Jan 1;70(1):208-17
references.pmid: 17657805
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W321-6
references.pmid: 15215403
references.citation: Biochemistry. 1991 Sep 3;30(35):8690-7
references.pmid: 1653605
references.citation: Annu Rev Biochem. 1989;58:951-98
references.pmid: 2673026
references.citation: Protein Eng. 2002 Jul;15(7):571-4
references.pmid: 12200539
references.citation: Proteins. 2009 Jun;75(4):787-98
references.pmid: 19003991
references.citation: J Biol Chem. 1989 Oct 5;264(28):16620-8
references.pmid: 2777802
references.citation: J Biol Chem. 1991 May 5;266(13):8050-4
references.pmid: 1902469
references.citation: Pac Symp Biocomput. 1998;:497-508
references.pmid: 9697207