title: SDM--a server for predicting effects of mutations on protein stability and malfunction.
abstract: The sheer volume of non-synonymous single nucleotide polymorphisms that have been generated in recent years from projects such as the Human Genome Project, the HapMap Project and Genome-Wide Association Studies means that it is not possible to characterize all mutations experimentally on the gene products, i.e. elucidate the effects of mutations on protein structure and function. However, automatic methods that can predict the effects of mutations will allow a reduced set of mutations to be studied. Site Directed Mutator (SDM) is a statistical potential energy function that uses environment-specific amino-acid substitution frequencies within homologous protein families to calculate a stability score, which is analogous to the free energy difference between the wild-type and mutant protein. Here, we present a web server for SDM (http://www-cryst.bioc.cam.ac.uk/~sdm/sdm.php), which has obtained more than 10,000 submissions since being online in April 2008. To run SDM, users must upload a wild-type structure and the position and amino acid type of the mutation. The results returned include information about the local structural environment of the wild-type and mutant residues, a stability score prediction and prediction of disease association. Additionally, the wild-type and mutant structures are displayed in a Jmol applet with the relevant residues highlighted.
authors: Biochemistry Department, University of Cambridge, Cambridge CB2 1GA, UK.
authors: Catherine L
authors: CL
authors: Worth
authors: Robert
authors: R
authors: Preissner
authors: Tom L
authors: TL
authors: Blundell
references: Nucleic Acids Res. 2003 Jul 1;31(13):3812-4
references: 12824425
references: Nat Rev Genet. 2010 Jan;11(1):31-46
references: 19997069
references: Bioinformatics. 2009 Oct 1;25(19):2537-43
references: 19654118
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D214-9
references: 21051339
references: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7406-11
references: 9636162
references: J Mol Biol. 1997 Sep 19;272(2):276-90
references: 9299354
references: J Mol Biol. 1971 Feb 14;55(3):379-400
references: 5551392
references: J Mol Biol. 1992 Jun 5;225(3):585-9
references: 1602471
references: Clin Endocrinol (Oxf). 2010 Nov;73(5):671-7
references: 20718767
references: Protein Eng Des Sel. 2008 Jan;21(1):19-27
references: 18093993
references: Biopolymers. 2006 May;82(1):80-92
references: 16453276
references: Bioinformatics. 2007 May 1;23(9):1099-105
references: 17341496
references: Protein Eng Des Sel. 2009 Feb;22(2):75-83
references: 19054789
references: J Biol Chem. 2008 Jan 18;283(3):1723-1731
references: 17974569
references: Nature. 2008 Apr 17;452(7189):872-6
references: 18421352
references: BMC Bioinformatics. 2007 Aug 20;8:301
references: 17708757
references: Protein Eng. 1997 Jan;10(1):7-21
references: 9051729
references: J Mol Biol. 2007 Sep 7;372(1):268-76
references: 17631895
references: Biochemistry. 2006 Oct 24;45(42):12673-9
references: 17042484
references: Nat Rev Genet. 2005 Sep;6(9):678-87
references: 16074985
references: Hum Mutat. 2001 Apr;17(4):263-70
references: 11295823
references: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D129-33
references: 14681376
references: J Mol Biol. 1993 Jan 5;229(1):194-220
references: 8421300
references: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references: 10592235
references: Structure. 2007 Dec;15(12):1567-76
references: 18073107
references: BMC Bioinformatics. 2005 Aug 25;6:207
references: 16122378
references: Annu Rev Physiol. 1995;57:43-68
references: 7778874
references: Bioinformatics. 2008 Sep 15;24(18):2002-9
references: 18632749
references: Biophys Chem. 2005 Apr 22;114(2-3):191-7
references: 15829352
references: Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9754-9
references: 15987780
references: Bioinformatics. 2005 Sep 1;21 Suppl 2:ii54-8
references: 16204125
references: J Mol Biol. 2002 Jul 5;320(2):369-87
references: 12079393
references: Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15069-74
references: 20696926
references: Proc Natl Acad Sci U S A. 1987 Jul;84(13):4441-4
references: 3299367
references: Science. 1987 May 1;236(4801):564-8
references: 3576184
references: Protein Sci. 1992 Feb;1(2):216-26
references: 1304904
references: Eur J Biochem. 1998 Oct 1;257(1):1-10
references: 9799096
references: Protein Sci. 1998 Nov;7(11):2469-71
references: 9828015
references: Methods Enzymol. 2006;410:359-76
references: 16938560
references: Curr Opin Struct Biol. 2009 Oct;19(5):596-604
references: 19765975
references: J Mol Biol. 2007 Sep 21;372(3):774-97
references: 17681537
references: J Mol Biol. 2002 Aug 9;321(2):285-96
references: 12144785
references: Protein Eng. 2003 Sep;16(9):665-71
references: 14560052
references: Protein Eng Des Sel. 2009 Sep;22(9):553-60
references: 19561092
references: Proc Biol Sci. 1990 Aug 22;241(1301):132-45
references: 1978340
references: J Mol Biol. 2004 Oct 1;342(5):1487-504
references: 15364576
references: Methods Mol Biol. 2010;609:97-112
references: 20221915
references: Proteins. 2004 Nov 1;57(2):400-13
references: 15340927
references: Eur J Biochem. 1991 Dec 18;202(3):715-28
references: 1765088
references: Hum Mutat. 2010 Jun;31(6):675-84
references: 20232415
references: Proteins. 2009 May 1;75(2):413-29
references: 18837037
references: J Neurochem. 2009 Jul;110(2):719-33
references: 19457084
references: Science. 2001 Feb 16;291(5507):1304-51
references: 11181995
references: Nature. 2007 Oct 18;449(7164):851-61
references: 17943122
references: Mol Cancer. 2008 Jun 09;7:53
references: 18541010
references: Hum Mutat. 2010 Jan;31(1):41-51
references: 19802898
references: J Biol Chem. 2005 Mar 18;280(11):10607-13
references: 15611128
references: J Biol Chem. 2009 Sep 18;284(38):25742-8
references: 19509286
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W239-42
references: 16845001
references: Hum Mol Genet. 2010 Feb 15;19(4):697-706
references: 19955118
references: J Bioinform Comput Biol. 2007 Dec;5(6):1297-318
references: 18172930
references: J Biol Chem. 2010 Jun 25;285(26):20080-7
references: 20378548
references: Acc Chem Res. 2000 Dec;33(12):889-97
references: 11123888
references: Proteins. 2006 Mar 1;62(4):1125-32
references: 16372356
references: Nat Struct Mol Biol. 2004 Oct;11(10):945-9
references: 15334070
references: J Biol Chem. 2006 Aug 25;281(34):24216-26
references: 16760466
references: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W306-10
references: 15980478
references: Proteins. 2009 Oct;77(1):84-96
references: 19408298
references: Proteins. 2005 Dec 1;61(4):704-21
references: 16231289
references: Bioinformatics. 2004 Aug 4;20 Suppl 1:i63-8
references: 15262782
references: Protein Eng. 1993 Apr;6(3):289-95
references: 8506263