title: Atomistic view of the conformational activation of Src kinase using the string method with swarms-of-trajectories.
abstract: The inactive-to-active conformational transition of the catalytic domain of human c-Src tyrosine kinase is characterized using the string method with swarms-of-trajectories with all-atom explicit solvent molecular dynamics simulations. The activation process occurs in two main steps in which the activation loop (A-loop) opens first, followed by the rotation of the alphaC helix. The computed potential of mean force energy along the activation pathway displays a local minimum, which allows the identification of an intermediate state. These results show that the string method with swarms-of-trajectories is an effective technique to characterize complex and slow conformational transitions in large biomolecular systems.
authors.forename: Wenxun
authors.initials: W
authors.lastname: Gan
authors.forename: Sichun
authors.initials: S
authors.lastname: Yang
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
mesh_terms: D001665:Binding Sites; D000081247:CSK Tyrosine-Protein Kinase; D002384:Catalysis; D003198:Computer Simulation; D004789:Enzyme Activation; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000648:ultrastructure*; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D019061:src-Family Kinases
chemical_list: D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human
references.citation: Structure. 2005 Jun;13(6):861-71
references.pmid: 15939018
references.citation: J Phys Chem B. 2005 Apr 14;109(14):6688-93
references.pmid: 16851751
references.citation: Proteins. 2007 Jun 1;67(4):1096-112
references.pmid: 17380483
references.citation: J Phys Chem B. 2008 Mar 20;112(11):3432-40
references.pmid: 18290641
references.citation: Mol Cell. 1999 May;3(5):629-38
references.pmid: 10360179
references.citation: J Am Chem Soc. 2009 Jan 14;131(1):244-50
references.pmid: 19067513
references.citation: Structure. 2005 Nov;13(11):1715-23
references.pmid: 16271895
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):139-44
references.pmid: 19109437
references.citation: Protein Sci. 2006 May;15(5):1051-62
references.pmid: 16597828
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14559-64
references.pmid: 17726097
references.citation: Oncogene. 2004 Oct 18;23(48):7906-9
references.pmid: 15489908
references.citation: PLoS Comput Biol. 2008 Mar 28;4(3):e1000047
references.pmid: 18369437
references.citation: Proteins. 2009 Feb 1;74(2):378-89
references.pmid: 18623061
references.citation: J Chem Phys. 2006 Jul 14;125(2):24106
references.pmid: 16848576
references.citation: Cell. 2001 Apr 6;105(1):115-26
references.pmid: 11301007
references.citation: Oncogene. 1993 Aug;8(8):2025-31
references.pmid: 8336932
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3776-81
references.pmid: 19225111
references.citation: Protein Sci. 2008 Nov;17(11):1871-80
references.pmid: 18687871