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Kabsch","year":"1983","journal-title":"Biopolymers"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/S0076-6879(96)66034-0","article-title":"GOR method for predicting protein secondary structure from amino acid sequence","volume":"266","author":"J Garnier","year":"1996","journal-title":"Computer Methods for Macromolecular Sequence Analysis"},{"key":"ref58","first-page":"681","article-title":"SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments","volume":"11","author":"C Geourjon","year":"1995","journal-title":"Comput Appl Biosci"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/protein\/6.8.849","article-title":"Quantification of Secondary Structure Prediction Improvement Using Multiple Alignments","volume":"6","author":"JM Levin","year":"1993","journal-title":"Protein 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Biol"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ceb.2007.02.010","article-title":"Receptor tyrosine kinases: mechanisms of activation and signaling","volume":"19","author":"SR Hubbard","year":"2007","journal-title":"Curr Opin Cell Biol"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1016\/j.str.2005.09.005","article-title":"The N-terminal end of the catalytic domain of SRC kinase Hck is a conformational switch implicated in long-range allosteric regulation","volume":"13","author":"NK Banavali","year":"2005","journal-title":"Structure"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1002\/prot.21334","article-title":"Anatomy of a structural pathway for activation of the catalytic domain of Src kinase Hck","volume":"67","author":"NK Banavali","year":"2007","journal-title":"Proteins"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"13643","DOI":"10.1073\/pnas.0704041104","article-title":"On the importance of a funneled energy landscape for the assembly and regulation of multidomain Src tyrosine kinases","volume":"104","author":"JD Faraldo-Gomez","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"e1000047","DOI":"10.1371\/journal.pcbi.1000047","article-title":"Src kinase conformational activation: thermodynamics, pathways, and mechanisms","volume":"4","author":"S Yang","year":"2008","journal-title":"PLoS Comput Biol"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/prot.22153","article-title":"Flexibility and charge asymmetry in the activation loop of Src tyrosine kinases","volume":"74","author":"NK Banavali","year":"2009","journal-title":"Proteins"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"3776","DOI":"10.1073\/pnas.0808261106","article-title":"Mapping the conformational transition in Src activation by cumulating the information from multiple molecular dynamics trajectories","volume":"106","author":"S Yang","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"L8","DOI":"10.1016\/j.bpj.2009.06.016","article-title":"Atomistic view of the conformational activation of Src kinase using the string method with swarms-of-trajectories","volume":"97","author":"W Gan","year":"2009","journal-title":"Biophys J"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jmgm.2004.06.001","article-title":"In silico activation of Src tyrosine kinase reveals the molecular basis for intramolecular autophosphorylation","volume":"23","author":"J Mendieta","year":"2004","journal-title":"J Mol Graph Model"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1110\/ps.051999206","article-title":"Src kinase activation: A switched electrostatic network","volume":"15","author":"E Ozkirimli","year":"2006","journal-title":"Protein Sci"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1110\/ps.037457.108","article-title":"An electrostatic network and long-range regulation of Src kinases","volume":"17","author":"E Ozkirimli","year":"2008","journal-title":"Protein Sci"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1073\/pnas.0811223106","article-title":"A conserved protonation-dependent switch controls drug binding in the Abl kinase","volume":"106","author":"YB Shan","year":"2009","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1021\/ja806846q","article-title":"Protein conformational transitions: the closure mechanism of a kinase explored by atomistic simulations","volume":"131","author":"A Berteotti","year":"2009","journal-title":"J Am Chem Soc"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1073\/pnas.0813266106","article-title":"Ligand-induced global transitions in the catalytic domain of protein kinase A","volume":"106","author":"C Hyeon","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1021\/ci100076j","article-title":"Molecular dynamics simulations and elastic network analysis of protein kinase B (Akt\/PKB) inactivation","volume":"50","author":"S Cheng","year":"2010","journal-title":"J Chem Inf Model"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1016\/j.bpj.2008.10.041","article-title":"Computational Modeling of Structurally Conserved Cancer Mutations in the RET and MET Kinases: The Impact on Protein Structure, Dynamics, and Stability","volume":"96","author":"A Dixit","year":"2009","journal-title":"Biophysical Journal"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"18496","DOI":"10.1073\/pnas.0706443104","article-title":"Large-scale allosteric conformational transitions of adenylate kinase appear to involve a population-shift mechanism","volume":"104","author":"K Arora","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"e1002179","DOI":"10.1371\/journal.pcbi.1002179","article-title":"Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases","volume":"7","author":"A Dixit","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref100","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000487","article-title":"Hierarchical Modeling of Activation Mechanisms in the ABL and EGFR Kinase Domains: Thermodynamic and Mechanistic Catalysts of Kinase Activation by Cancer Mutations","volume":"5","author":"A Dixit","year":"2009","journal-title":"Plos Computational Biology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/prot.22862","article-title":"Conformational regulation of the EGFR kinase core by the juxtamembrane and C-terminal tail: a molecular dynamics study","volume":"79","author":"M Mustafa","year":"2011","journal-title":"Proteins"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/prot.22353","article-title":"Conformational dynamics of the EGFR kinase domain reveals structural features involved in activation","volume":"76","author":"A Papakyriakou","year":"2009","journal-title":"Proteins"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1002\/jcc.21866","article-title":"Molecular dynamics simulation reveals structural and thermodynamic features of kinase activation by cancer mutations within the epidermal growth factor receptor","volume":"32","author":"S Wan","year":"2011","journal-title":"J Comput Chem"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1016\/j.cell.2006.05.013","article-title":"An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor","volume":"125","author":"X Zhang","year":"2006","journal-title":"Cell"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/prot.21928","article-title":"Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process","volume":"72","author":"J Zou","year":"2008","journal-title":"Proteins-Structure Function and Bioinformatics"},{"key":"ref106","article-title":"Molecular dynamics simulations of a mutant back to normal prove reversibility of the mutation-induced effects in KIT","author":"N Panel","year":"2014","journal-title":"Manuscript in preparation"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/pro.347","article-title":"Drug binding and resistance mechanism of KIT tyrosine kinase revealed by hydrogen\/deuterium exchange FTICR mass spectrometry","volume":"19","author":"HM Zhang","year":"2010","journal-title":"Protein Sci"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"31461","DOI":"10.1074\/jbc.C300186200","article-title":"Structure of a c-Kit product complex reveals the basis for kinase transactivation","volume":"278","author":"CD Mol","year":"2003","journal-title":"Journal of Biological Chemistry"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/jid.2009.448","article-title":"Mastocytosis in children is associated with mutations in c-KIT","volume":"130","author":"CJ Price","year":"2010","journal-title":"J Invest Dermatol"},{"key":"ref110","first-page":"920","article-title":"KIT activating mutations: incidence in adult and pediatric acute myeloid leukemia, and identification of an internal tandem duplication","volume":"89","author":"A Beghini","year":"2004","journal-title":"Haematologica"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1200\/JCO.2006.06.2984","article-title":"Somatic activation of KIT in distinct subtypes of melanoma","volume":"24","author":"JA Curtin","year":"2006","journal-title":"J Clin Oncol"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1038\/nrc1434","article-title":"Switching on kinases: oncogenic activation of BRAF and the PDGFR family","volume":"4","author":"NJ Dibb","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"e97519","DOI":"10.1371\/journal.pone.0097519","article-title":"Differential effects of CSF-1R D802V and KIT D816V homologous mutations on receptor tertiary structure and allosteric communication","volume":"9","author":"P Gomez Da Silva Figueiredo Celestino","year":"2014","journal-title":"PLoS ONE"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"026001","DOI":"10.1088\/1478-3975\/5\/2\/026001","article-title":"Discrete breathers in protein structures","volume":"5","author":"F Piazza","year":"2008","journal-title":"Phys Biol"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"046014","DOI":"10.1088\/1478-3975\/6\/4\/046014","article-title":"Long-range energy transfer in proteins","volume":"6","author":"F Piazza","year":"2009","journal-title":"Phys Biol"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"16984","DOI":"10.1073\/pnas.0906510106","article-title":"Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins","volume":"106","author":"TP Schrank","year":"2009","journal-title":"Proc Natl Acad Sci U S 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