title: C(α) torsion angles as a flexible criterion to extract secrets from a molecular dynamics simulation.
abstract: Given the increasing complexity of simulated molecular systems, and the fact that simulation times have now reached milliseconds to seconds, immense amounts of data (in the gigabyte to terabyte range) are produced in current molecular dynamics simulations. Manual analysis of these data is a very time-consuming task, and important events that lead from one intermediate structure to another can become occluded in the noise resulting from random thermal fluctuations. To overcome these problems and facilitate a semi-automated data analysis, we introduce in this work a measure based on C(α) torsion angles: torsion angles formed by four consecutive C(α) atoms. This measure describes changes in the backbones of large systems on a residual length scale (i.e., a small number of residues at a time). Cluster analysis of individual C(α) torsion angles and its fuzzification led to continuous time patches representing (meta)stable conformations and to the identification of events acting as transitions between these conformations. The importance of a change in torsion angle to structural integrity is assessed by comparing this change to the average fluctuations in the same torsion angle over the complete simulation. Using this novel measure in combination with other measures such as the root mean square deviation (RMSD) and time series of distance measures, we performed an in-depth analysis of a simulation of the open form of DNA polymerase I. The times at which major conformational changes occur and the most important parts of the molecule and their interrelations were pinpointed in this analysis. The simultaneous determination of the time points and localizations of major events is a significant advantage of the new bottom-up approach presented here, as compared to many other (top-down) approaches in which only the similarity of the complete structure is analyzed.
authors.affiliation: Department of Chemistry, Konstanz Research School Chemical Biology, and Zukunftskolleg, University of Konstanz, 78457, Konstanz, Germany, Fredrick.Devadoss@uni-konstanz.de.
authors.forename: Fredrick Robin Devadoss
authors.initials: FR
authors.lastname: Victor Paul Raj
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Exner
mesh_terms: D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
references.citation: J Am Chem Soc. 2012 Jul 25;134(29):11840-3
references.pmid: 22475415
references.citation: J Med Chem. 2005 May 5;48(9):3214-20
references.pmid: 15857127
references.citation: Curr Opin Struct Biol. 2006 Feb;16(1):71-8
references.pmid: 16413772
references.citation: Adv Protein Chem. 2005;71:401-40
references.pmid: 16230118
references.citation: Biophys J. 2010 Nov 17;99(10):3463-72
references.pmid: 21081096
references.citation: Biophys J. 2012 Aug 22;103(4):786-96
references.pmid: 22947940
references.citation: Biochemistry. 1997 Feb 4;36(5):1100-7
references.pmid: 9033400
references.citation: Structure. 2012 Apr 4;20(4):618-27
references.pmid: 22483109
references.citation: Biochem Biophys Res Commun. 2006 Sep 1;347(3):626-33
references.pmid: 16842743
references.citation: J Nucleic Acids. 2010 Aug 22;2010:
references.pmid: 20847947
references.citation: Biochim Biophys Acta. 2010 May;1804(5):1064-80
references.pmid: 19733263
references.citation: J Comput Chem. 2011 Jul 30;32(10):2319-27
references.pmid: 21500218
references.citation: J Comput Chem. 2006 Nov 15;27(14):1765-8
references.pmid: 16917862
references.citation: J Am Chem Soc. 2003 Jul 9;125(27):8163-77
references.pmid: 12837086
references.citation: J Chem Phys. 2011 May 7;134(17):174105
references.pmid: 21548671
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6620-5
references.pmid: 19351898
references.citation: J Chem Theory Comput. 2009 Oct 13;5(10):2595-605
references.pmid: 26631775
references.citation: Org Biomol Chem. 2004 Nov 21;2(22):3219-21
references.pmid: 15534698
references.citation: J Chem Inf Model. 2012 Jan 23;52(1):255-9
references.pmid: 22191855
references.citation: J Mol Biol. 2005 Sep 30;352(4):807-22
references.pmid: 16139299
references.citation: J Phys Chem B. 2012 Jul 26;116(29):8722-31
references.pmid: 22494262
references.citation: DNA Repair (Amst). 2008 Nov 1;7(11):1824-34
references.pmid: 18692600
references.citation: Biophys J. 2004 Jun;86(6):3392-408
references.pmid: 15189842
references.citation: J Am Chem Soc. 2004 Jul 14;126(27):8441-53
references.pmid: 15238001
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: Phys Chem Chem Phys. 2011 Jun 14;13(22):10421-5
references.pmid: 21465020
references.citation: J Mol Biol. 2007 Apr 20;368(1):18-29
references.pmid: 17321543
references.citation: J Comput Chem. 2013 Feb 5;34(4):319-25
references.pmid: 23047307
references.citation: Biopolymers. 2003 Mar;68(3):286-99
references.pmid: 12601790
references.citation: Biochem J. 1998 Apr 1;331 ( Pt 1):79-87
references.pmid: 9512464
references.citation: Protein Sci. 2010 Apr;19(4):815-25
references.pmid: 20162624
references.citation: Protein Sci. 1995 Oct;4(10):2118-22
references.pmid: 8535248
references.citation: J Comput Chem. 2005 Dec;26(16):1781-802
references.pmid: 16222654
references.citation: Nucleic Acids Res. 2012 Feb;40(3):e25
references.pmid: 22139913
references.citation: Protein Eng. 1999 Sep;12(9):713-20
references.pmid: 10506280
references.citation: FEBS Lett. 2007 Feb 20;581(4):775-80
references.pmid: 17286973
references.citation: PLoS Comput Biol. 2013;9(5):e1003074
references.pmid: 23717197
references.citation: Angew Chem Int Ed Engl. 2005 Jul 25;44(30):4712-5
references.pmid: 15995989
references.citation: EMBO J. 1998 Dec 15;17(24):7514-25
references.pmid: 9857206
references.citation: J Chem Theory Comput. 2007 Nov;3(6):2312-34
references.pmid: 26636222
references.citation: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6819-24
references.pmid: 15863620
references.citation: J Chem Theory Comput. 2013 Jul 9;9(7):3084-95
references.pmid: 26583988
references.citation: J Chem Theory Comput. 2011 Mar 8;7(3):778-89
references.pmid: 26596308
references.citation: J Mol Biol. 2010 Dec 17;404(5):778-93
references.pmid: 20950625
references.citation: Biochemistry. 2005 Oct 11;44(40):13328-41
references.pmid: 16201758
references.citation: J Biol Chem. 2012 Apr 20;287(17):14099-108
references.pmid: 22318723
references.citation: J Comput Chem. 2009 Feb;30(3):479-92
references.pmid: 18680215
references.citation: J Chem Theory Comput. 2012 Aug 14;8(8):2930-7
references.pmid: 26592131
references.citation: J Mol Biol. 2002 Apr 12;317(5):651-71
references.pmid: 11955015
references.citation: J Chem Phys. 2007 Apr 21;126(15):155102
references.pmid: 17461666
references.citation: Chembiochem. 2012 Mar 19;13(5):635-9
references.pmid: 22315195
references.citation: Biochemistry. 1997 Sep 16;36(37):11205-15
references.pmid: 9287163
references.citation: J Mol Biol. 2002 Aug 16;321(3):459-78
references.pmid: 12162959
references.citation: J Chem Theory Comput. 2012 Oct 9;8(10):3810-9
references.pmid: 26593022
references.citation: Biophys J. 2004 Nov;87(5):3088-99
references.pmid: 15507687
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21327-31
references.pmid: 21123743
references.citation: J Chem Theory Comput. 2012 Apr 10;8(4):1176-1189
references.pmid: 22715321
references.citation: Biochemistry. 1992 Sep 29;31(38):9227-36
references.pmid: 1327109
references.citation: J Chem Theory Comput. 2012 Mar 13;8(3):1108-20
references.pmid: 26593370
references.citation: J Comput Chem. 2011 Apr 30;32(6):1183-94
references.pmid: 21387345
references.citation: BMC Biophys. 2012 Jun 07;5:11
references.pmid: 22676913
references.citation: Proc Natl Acad Sci U S A. 2005 Jan 18;102(3):628-33
references.pmid: 15644439
references.citation: J Phys Chem B. 2005 Mar 24;109(11):5358-67
references.pmid: 16863202