title: RosettaEPR: rotamer library for spin label structure and dynamics.
abstract: An increasingly used parameter in structural biology is the measurement of distances between spin labels bound to a protein. One limitation to these measurements is the unknown position of the spin label relative to the protein backbone. To overcome this drawback, we introduce a rotamer library of the methanethiosulfonate spin label (MTSSL) into the protein modeling program Rosetta. Spin label rotamers were derived from conformations observed in crystal structures of spin labeled T4 lysozyme and previously published molecular dynamics simulations. Rosetta's ability to accurately recover spin label conformations and EPR measured distance distributions was evaluated against 19 experimentally determined MTSSL labeled structures of T4 lysozyme and the membrane protein LeuT and 73 distance distributions from T4 lysozyme and the membrane protein MsbA. For a site in the core of T4 lysozyme, the correct spin label conformation (Χ1 and Χ2) is recovered in 99.8% of trials. In surface positions 53% of the trajectories agree with crystallized conformations in Χ1 and Χ2. This level of recovery is on par with Rosetta performance for the 20 natural amino acids. In addition, Rosetta predicts the distance between two spin labels with a mean error of 4.4 Å. The width of the experimental distance distribution, which reflects the flexibility of the two spin labels, is predicted with a mean error of 1.3 Å. RosettaEPR makes full-atom spin label modeling available to a wide scientific community in conjunction with the powerful suite of modeling methods within Rosetta.
authors.affiliation: Center for Structural Biology, Vanderbilt University, Nashville, Tennessee, United States of America ; Department of Chemistry, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Alexander
authors.forename: Richard A
authors.initials: RA
authors.lastname: Stein
authors.forename: Hanane A
authors.initials: HA
authors.lastname: Koteiche
authors.forename: Kristian W
authors.initials: KW
authors.lastname: Kaufmann
authors.forename: Hassane S
authors.initials: HS
authors.lastname: McHaourab
authors.forename: Jens
authors.initials: J
authors.lastname: Meiler
mesh_terms: D017122:Bacteriophage T4 / Q000201:enzymology; D004578:Electron Spin Resonance Spectroscopy; D008698:Mesylates / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D012984:Software; D013113:Spin Labels
chemical_list: D008698:Mesylates; D011506:Proteins; D013113:Spin Labels; C074502:methanethiosulfonate; D009113:Muramidase
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8239-43
references.pmid: 7667275
references.citation: J Magn Reson. 2004 Jul;169(1):1-12
references.pmid: 15183350
references.citation: Structure. 2011 Nov 9;19(11):1549-61
references.pmid: 22078555
references.citation: Nature. 2007 Nov 8;450(7167):259-64
references.pmid: 17934447
references.citation: Structure. 2011 Jun 8;19(6):844-58
references.pmid: 21645855
references.citation: J Struct Biol. 2011 Mar;173(3):549-57
references.pmid: 21074624
references.citation: Proteins. 2009 Dec;77(4):778-95
references.pmid: 19603484
references.citation: J Magn Reson. 2002 May;156(1):104-12
references.pmid: 12081447
references.citation: J Magn Reson. 2005 Feb;172(2):279-95
references.pmid: 15649755
references.citation: Appl Magn Reson. 2012 Apr;42(3):377-391
references.pmid: 22448103
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10383-8
references.pmid: 10984534
references.citation: Phys Chem Chem Phys. 2011 Feb 14;13(6):2356-66
references.pmid: 21116569
references.citation: Science. 2010 Feb 19;327(5968):1014-8
references.pmid: 20133520
references.citation: Structure. 2011 Apr 13;19(4):441-3
references.pmid: 21481766
references.citation: Proteins. 2003 Oct 1;53(1):76-87
references.pmid: 12945051
references.citation: J Struct Biol. 2011 Mar;173(3):506-14
references.pmid: 21029778
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9420-4
references.pmid: 21606326
references.citation: J Mol Biol. 2008 Sep 5;381(3):670-80
references.pmid: 18582475
references.citation: Biophys J. 2009 Jan;96(1):217-25
references.pmid: 19134477
references.citation: Protein Sci. 2009 May;18(5):893-908
references.pmid: 19384990
references.citation: Proteins. 2000 Aug 15;40(3):389-408
references.pmid: 10861930
references.citation: Biochemistry. 2010 Nov 30;49(47):10045-60
references.pmid: 20964375
references.citation: Curr Opin Struct Biol. 2002 Aug;12(4):431-40
references.pmid: 12163064
references.citation: Acta Biochim Pol. 2007;54(2):235-44
references.pmid: 17565387
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Protein Sci. 2007 Jun;16(6):1069-86
references.pmid: 17473014
references.citation: Proteins. 2005 Apr 1;59(1):15-29
references.pmid: 15690346
references.citation: J Mol Biol. 1987 Jan 5;193(1):189-99
references.pmid: 3586019
references.citation: Protein Sci. 2008 Feb;17(2):228-39
references.pmid: 18096642
references.citation: Phys Chem Chem Phys. 2007 Apr 28;9(16):1895-910
references.pmid: 17431518
references.citation: J Phys Chem B. 2006 Dec 28;110(51):26248-59
references.pmid: 17181283
references.citation: Structure. 2008 Feb;16(2):181-95
references.pmid: 18275810
references.citation: Science. 2005 Sep 16;309(5742):1868-71
references.pmid: 16166519
references.citation: J Am Chem Soc. 2007 Nov 14;129(45):13840-6
references.pmid: 17948993
references.citation: Science. 1989 Feb 10;243(4892):792-4
references.pmid: 2916125
references.citation: Protein Sci. 2005 May;14(5):1328-39
references.pmid: 15802647
references.citation: Nat Struct Mol Biol. 2010 Jul;17(7):822-9
references.pmid: 20562855
references.citation: Biochemistry. 2000 Jul 25;39(29):8396-405
references.pmid: 10913245
references.citation: J Mol Model. 2009 Sep;15(9):1093-108
references.pmid: 19234730
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19005-10
references.pmid: 18024585
references.citation: J Mol Biol. 2009 Oct 30;393(3):586-97
references.pmid: 19715702
references.citation: Bioinformatics. 2003 Aug 12;19(12):1589-91
references.pmid: 12912846
references.citation: J Am Chem Soc. 2002 May 15;124(19):5304-14
references.pmid: 11996571
references.citation: J Am Chem Soc. 2005 Jul 6;127(26):9334-5
references.pmid: 15984837
references.citation: Science. 2003 Nov 21;302(5649):1364-8
references.pmid: 14631033
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 2;104(40):15682-7
references.pmid: 17905872
references.citation: PLoS Biol. 2007 Oct;5(10):e271
references.pmid: 17927448