title: Dissecting protein architecture with communication blocks and communicating segment pairs.
abstract: BACKGROUND
  Proteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary to understand how proteins function. Given a conformational ensemble, computational tools are needed to extract in a systematic way pertinent and comprehensive biological information.
  
  
  RESULTS
  Here, we present a method, Communication Mapping (COMMA), to decipher the dynamical architecture of a protein. The method first extracts residue-based dynamic properties from all-atom molecular dynamics simulations. Then, it integrates them in a graph theoretic framework, where it identifies groups of residues or protein regions that mediate short- and long-range communication. COMMA introduces original concepts to contrast the different roles played by these regions, namely communication blocks and communicating segment pairs, and evaluates the connections and communication strengths between them. We show the utility and capabilities of COMMA by applying it to three archetypal proteins, namely protein A, the tyrosine kinase KIT and the tumour suppressor p53.
  
  
  CONCLUSIONS
  Our method permits to compare in a direct way the dynamical behaviour either of proteins with different characteristics or of the same protein in different conditions. It is useful to identify residues playing a key role in protein allosteric regulation and to explain the effects of deleterious mutations in a mechanistic way. COMMA is a fully automated tool with broad applicability. It is freely available to the community at www.lcqb.upmc.fr/COMMA .
authors.affiliation: Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l'Ecole de Médecine, Paris, 75006, France. Yasaman.Karami@upmc.fr.|Sorbonne Universités, UPMC Univ Paris 06, ICS, Paris, 75005, France. Yasaman.Karami@upmc.fr.
authors.forename: Yasaman
authors.initials: Y
authors.lastname: Karami
authors.affiliation: Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l'Ecole de Médecine, Paris, 75006, France. elodie.laine@upmc.fr.
authors.forename: Elodie
authors.initials: E
authors.lastname: Laine
authors.affiliation: Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l'Ecole de Médecine, Paris, 75006, France. Alessandra.Carbone@lip6.fr.|Institut Universitaire de France, Paris, 75005, France. Alessandra.Carbone@lip6.fr.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carbone
mesh_terms: D000494:Allosteric Regulation; D001331:Automation; D006801:Humans; D056004:Molecular Dynamics Simulation; D009038:Motion; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry; D012984:Software; D013205:Staphylococcal Protein A / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry
chemical_list: D011506:Proteins; D013205:Staphylococcal Protein A; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit
references.citation: Annu Rev Biophys. 2012;41:429-52
references.pmid: 22577825
references.citation: Biochemistry. 2007 Mar 13;46(10):2630-9
references.pmid: 17297920
references.citation: Science. 1991 Dec 13;254(5038):1598-603
references.pmid: 1749933
references.citation: Cell. 2010 Jun 25;141(7):1117-34
references.pmid: 20602996
references.citation: J Chem Theory Comput. 2009 Oct 13;5(10):2595-605
references.pmid: 26631775
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references.pmid: 10592235
references.citation: J Chem Phys. 2008 Jun 21;128(23):235105
references.pmid: 18570534
references.citation: PLoS Comput Biol. 2007 Sep;3(9):1716-26
references.pmid: 17892319
references.citation: Br J Haematol. 2007 Jul;138(1):12-30
references.pmid: 17555444
references.citation: Proteins. 2006 Aug 1;64(2):391-403
references.pmid: 16700056
references.citation: FEBS Lett. 2007 Jun 19;581(15):2776-82
references.pmid: 17531981
references.citation: J Mol Biol. 1994 May 20;238(5):777-93
references.pmid: 8182748
references.citation: Eur J Cancer. 2002 Sep;38 Suppl 5:S39-51
references.pmid: 12528772
references.citation: Protein Sci. 2013 Oct;22(10):1399-416
references.pmid: 23934896
references.citation: Biophys J. 2005 Dec;89(6):4159-70
references.pmid: 16150969
references.citation: Curr Protein Pept Sci. 2009 Apr;10(2):146-60
references.pmid: 19355982
references.citation: Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):E4623-31
references.pmid: 25319261
references.citation: Curr Opin Struct Biol. 2014 Feb;24:98-105
references.pmid: 24463371
references.citation: Int J Biochem Cell Biol. 2007;39(11):1995-8
references.pmid: 17350321
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D292-6
references.pmid: 24153109
references.citation: Cell. 2009 May 1;137(3):413-31
references.pmid: 19410540
references.citation: J Mol Biol. 2008 Apr 18;378(1):1-11
references.pmid: 18353365
references.citation: PLoS Comput Biol. 2011 Jun;7(6):e1002068
references.pmid: 21698178
references.citation: Biopolymers. 1983 Dec;22(12):2577-637
references.pmid: 6667333
references.citation: Nat Rev Cancer. 2009 Oct;9(10 ):758-62
references.pmid: 19776745
references.citation: PLoS One. 2013 Nov 12;8(11):e80221
references.pmid: 24324553
references.citation: J Chem Inf Model. 2014 May 27;54(5):1537-51
references.pmid: 24702124
references.citation: BMC Bioinformatics. 2014 Dec 10;15:399
references.pmid: 25491031
references.citation: Curr Opin Struct Biol. 2009 Apr;19(2):197-202
references.pmid: 19286366
references.citation: Cell. 2012 Jun 8;149(6):1269-83
references.pmid: 22682249
references.citation: Biophys J. 2015 Oct 20;109 (8):1528-32
references.pmid: 26488642
references.citation: PLoS One. 2013 Aug 19;8(8):e71936
references.pmid: 23977182
references.citation: J Chem Theory Comput. 2013 May 14;9(5):2504-18
references.pmid: 26583738
references.citation: Curr Opin Struct Biol. 2003 Dec;13(6):748-57
references.pmid: 14675554
references.citation: Protein Sci. 1997 Jul;6(7):1449-57
references.pmid: 9232646
references.citation: Cell. 2002 May 3;109(3):275-82
references.pmid: 12015977
references.citation: PLoS Comput Biol. 2012;8(12):e1002844
references.pmid: 23300424
references.citation: Biochemistry. 2004 Mar 30;43(12):3582-9
references.pmid: 15035628
references.citation: Faraday Discuss. 2014;169:303-21
references.pmid: 25340971
references.citation: J Mol Biol. 2006 Jul 21;360(4):850-64
references.pmid: 16782128
references.citation: PLoS Comput Biol. 2011 Oct;7(10):e1002179
references.pmid: 21998569
references.citation: Annu Rev Biophys Biomol Struct. 2000;29:291-325
references.pmid: 10940251
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1542-7
references.pmid: 19164557
references.citation: EMBO J. 1988 Apr;7(4):1003-11
references.pmid: 2456920
references.citation: Nat Commun. 2015 Jan 20;6:5939
references.pmid: 25600932
references.citation: Mol Cell. 2007 Sep 7;27(5):717-30
references.pmid: 17803937
references.citation: Biochem Biophys Res Commun. 2005 Dec 23;338(3):1307-15
references.pmid: 16226710
references.citation: Nature. 2007 Dec 13;450(7172):964-72
references.pmid: 18075575
references.citation: Biochemistry. 1972 Feb 29;11(5):864-78
references.pmid: 5059892
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14338-42
references.pmid: 9405613
references.citation: J Mol Biol. 1965 May;12 :88-118
references.pmid: 14343300
references.citation: Mol Cell. 2004 Jan 30;13(2):169-78
references.pmid: 14759363
references.citation: Biopolymers. 1992 May;32(5):523-35
references.pmid: 1515543
references.citation: J Comput Chem. 2011 Apr 30;32(6):1183-94
references.pmid: 21387345
references.citation: PLoS Comput Biol. 2012;8(8):e1002661
references.pmid: 22927810
references.citation: PLoS Comput Biol. 2014 Sep 04;10(9):e1003744
references.pmid: 25187961
references.citation: Mol Cell. 2004 Sep 10;15(5):661-75
references.pmid: 15350212
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 14;103(7):2109-14
references.pmid: 16461916
references.citation: PLoS One. 2012;7(4):e35686
references.pmid: 22558199
references.citation: Biophys J. 2006 Jul 1;91(1):164-72
references.pmid: 16617086
references.citation: Proc Natl Acad Sci U S A. 2004 May 4;101(18):6952-6
references.pmid: 15069202
references.citation: Nature. 2000 Nov 16;408(6810):307-10
references.pmid: 11099028
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):16984-9
references.pmid: 19805185
references.citation: Bioinformatics. 2013 Aug 15;29(16):2053-5
references.pmid: 23740748
references.citation: Biochemistry. 2003 Mar 4;42(8):2396-403
references.pmid: 12600206
references.citation: PLoS Comput Biol. 2014 Jul 31;10(7):e1003749
references.pmid: 25079768