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allosteric shape-shifting","volume":"439","author":"CJ Tsai","year":"2011","journal-title":"Biochem J"},{"issue":"12","key":"ref86","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.tips.2011.08.004","article-title":"Allo-network drugs: harnessing allostery in cellular networks","volume":"32","author":"R Nussinov","year":"2011","journal-title":"Trends Pharmacol Sci"},{"issue":"5","key":"ref87","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1124\/mol.114.094342","article-title":"Advances in G protein-coupled receptor allostery: from function to structure","volume":"86","author":"A Christopoulos","year":"2014","journal-title":"Mol Pharmacol"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"675382","DOI":"10.1155\/2013\/675382","article-title":"Mutations in MC1R Gene Determine Black Coat Color Phenotype in Chinese Sheep","volume":"2013","author":"G-L Yang","year":"2013","journal-title":"Sci World J"},{"issue":"6125","key":"ref89","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1126\/science.1233213","article-title":"Adaptive Evolution of Multiple Traits Through Multiple Mutations at a Single Gene","volume":"339","author":"CR Linnen","year":"2013","journal-title":"Science"},{"issue":"10","key":"ref90","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.tibs.2012.07.001","article-title":"Allosteric post-translational modification codes","volume":"37","author":"R Nussinov","year":"2012","journal-title":"Trends Biochem Sci"},{"issue":"9","key":"ref91","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.cub.2016.03.008","article-title":"The MC1R Gene and Youthful Looks","volume":"26","author":"F Liu","year":"2016","journal-title":"Curr Biol"},{"issue":"3","key":"ref92","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ng1195-328","article-title":"Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans","volume":"11","author":"P Valverde","year":"1995","journal-title":"Nat Genet"},{"issue":"11","key":"ref93","doi-asserted-by":"crossref","first-page":"e28145","DOI":"10.1371\/journal.pone.0028145","article-title":"Detecting low frequent loss-of-function alleles in genome wide association studies with red hair color as example","volume":"6","author":"F Liu","year":"2011","journal-title":"PLoS One"},{"issue":"7","key":"ref94","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1038\/jid.2015.62","article-title":"A Genome-Wide Association Study Identifies the Skin Color Genes IRF4, MC1R, ASIP, and BNC2 Influencing Facial Pigmented Spots","volume":"135","author":"LC Jacobs","year":"2015","journal-title":"J Invest Dermatol"},{"issue":"24","key":"ref95","doi-asserted-by":"crossref","first-page":"1800","DOI":"10.1136\/heartjnl-2013-303939","article-title":"A systematic review and meta-analysis of genotype-phenotype associations in patients with hypertrophic cardiomyopathy caused by sarcomeric protein mutations","volume":"99","author":"LR Lopes","year":"2013","journal-title":"Heart"},{"issue":"4","key":"ref96","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/mgg3.68","article-title":"Mutation spectrum and genotype-phenotype correlations in a large French cohort of MYH9-Related Disorders","volume":"2","author":"B Saposnik","year":"2014","journal-title":"Mol Genet Genomic Med"},{"issue":"2","key":"ref97","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nbt.2106","article-title":"Three-dimensional reconstruction of protein networks provides insight into human genetic disease","volume":"30","author":"X Wang","year":"2012","journal-title":"Nat Biotechnol"},{"issue":"0","key":"ref98","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.sbi.2015.01.004","article-title":") \u2018Latent drivers\u2019 expand the cancer mutational landscape","volume":"32","author":"R Nussinov","year":"2015","journal-title":"Curr Opin Struct Biol"},{"issue":"6","key":"ref99","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1124\/mol.114.091736","article-title":"Pro32Pro33 Mutations in the Integrin beta(3) PSI Domain Result in alpha IIb beta(3) Priming and Enhanced Adhesion: Reversal of the Hypercoagulability Phenotype by the Src Inhibitor SKI-606","volume":"85","author":"KH Oliver","year":"2014","journal-title":"Mol Pharmacol"},{"issue":"11","key":"ref100","doi-asserted-by":"crossref","first-page":"e47304","DOI":"10.1371\/journal.pone.0047304","article-title":"Modeling and Molecular Dynamics of HPA-1a and-1b Polymorphisms: Effects on the Structure of the beta 3 Subunit of the alpha IIb beta 3 Integrin","volume":"7","author":"V Jallu","year":"2012","journal-title":"Plos One"},{"issue":"10","key":"ref101","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1002\/humu.22621","article-title":"Gain-of-Function Mutation in STIM1 (P.R304W) Is Associated with Stormorken Syndrome","volume":"35","author":"G Morin","year":"2014","journal-title":"Hum Mutat"},{"issue":"15","key":"ref102","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1016\/j.bmcl.2014.05.064","article-title":"Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein","volume":"24","author":"K Ohgane","year":"2014","journal-title":"Bioorganic Med Chem Lett"},{"issue":"35","key":"ref103","doi-asserted-by":"crossref","first-page":"24397","DOI":"10.1074\/jbc.M114.589911","article-title":"Expanding the Proteome of an RNA Virus by Phosphorylation of an Intrinsically Disordered Viral Protein","volume":"289","author":"DG Cordek","year":"2014","journal-title":"J Biol Chem"},{"issue":"1","key":"ref104","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nsmb.2924","article-title":"Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation","volume":"22","author":"N Thevakumaran","year":"2015","journal-title":"Nat Struct Mol Biol"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.semcdb.2016.04.001","article-title":"Oncogenic KRAS signaling and YAP1\/beta-catenin: Similar cell cycle control in tumor initiation","volume":"58","author":"R Nussinov","year":"2016","journal-title":"Semin Cell Dev Biol"},{"issue":"5","key":"ref106","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.tips.2017.02.001","article-title":"A New View of Pathway-Driven Drug Resistance in Tumor Proliferation","volume":"38","author":"R Nussinov","year":"2017","journal-title":"Trends Pharmacol Sci"},{"issue":"7377","key":"ref107","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/480329a","article-title":"CANCER A drug-resistant duo","volume":"480","author":"H Lavoie","year":"2011","journal-title":"Nature"},{"issue":"7377","key":"ref108","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature10662","article-title":"RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)","volume":"480","author":"PI Poulikakos","year":"2011","journal-title":"Nature"},{"issue":"4","key":"ref109","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1042\/BST20140070","article-title":"PI3K\/Akt-mediated regulation of p53 in cancer","volume":"42","author":"O Abraham AG","year":"2014","journal-title":"Biochem Soc Trans"},{"issue":"24","key":"ref110","doi-asserted-by":"crossref","first-page":"7161","DOI":"10.1158\/0008-5472.CAN-14-1446","article-title":"MDM2-p53 Pathway in Hepatocellular Carcinoma","volume":"74","author":"X Meng","year":"2014","journal-title":"Cancer Res"},{"issue":"17","key":"ref111","doi-asserted-by":"crossref","first-page":"i763","DOI":"10.1093\/bioinformatics\/btw464","article-title":"Edge-based sensitivity analysis of signaling networks by using Boolean dynamics","volume":"32","author":"HC Trinh","year":"2016","journal-title":"Bioinformatics"},{"issue":"3","key":"ref112","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1056\/NEJMoa1709449","article-title":"Somatic Activating KRAS Mutations in Arteriovenous Malformations of the Brain","volume":"378","author":"SI Nikolaev","year":"2018","journal-title":"N Engl J Med"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/msb.2009.80","article-title":"Edgetic perturbation models of human inherited disorders","volume":"5","author":"Q Zhong","year":"2009","journal-title":"Mol Syst Biol"},{"issue":"12","key":"ref114","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/ng.3138","article-title":"A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks","volume":"46","author":"M AlQuraishi","year":"2014","journal-title":"Nat Genet"},{"issue":"6","key":"ref115","doi-asserted-by":"crossref","first-page":"e66273","DOI":"10.1371\/journal.pone.0066273","article-title":"Cancer missense mutations alter binding properties of proteins and their interaction networks","volume":"8","author":"H Nishi","year":"2013","journal-title":"PLoS One"},{"issue":"4","key":"ref116","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.semcancer.2013.05.003","article-title":"The structural network of inflammation and cancer: merits and challenges","volume":"23","author":"E Guven Maiorov","year":"2013","journal-title":"Semin Cancer Biol"},{"issue":"2\u20133","key":"ref117","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jmb.2011.11.023","article-title":"Selective Molecular Recognition in Amyloid Growth and Transmission and Cross-Species Barriers","volume":"421","author":"B Ma","year":"2012","journal-title":"J Mol Biol"},{"issue":"8","key":"ref118","doi-asserted-by":"crossref","first-page":"4820","DOI":"10.1021\/cr900377t","article-title":"Polymorphism in Alzheimer A\u03b2 Amyloid Organization Reflects Conformational Selection in a Rugged Energy Landscape","volume":"110","author":"Y Miller","year":"2010","journal-title":"Chem Rev"},{"issue":"14","key":"ref119","doi-asserted-by":"crossref","first-page":"6332","DOI":"10.1039\/c3cp54253j","article-title":"The free energy landscape in translational science: how can somatic mutations result in constitutive oncogenic activation?","volume":"16","author":"CJ Tsai","year":"2014","journal-title":"Phys Chem Chem Phys"},{"issue":"10","key":"ref120","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1158\/0008-5472.CAN-11-2612","article-title":"A comprehensive survey of Ras mutations in cancer","volume":"72","author":"IA Prior","year":"2012","journal-title":"Cancer Res"},{"issue":"4","key":"ref121","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1073\/pnas.1119675109","article-title":"The mystery of missing heritability: Genetic interactions create phantom heritability","volume":"109","author":"O Zuk","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ref122","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/ng.2355","article-title":"Leveraging models of cell regulation and GWAS data in integrative network-based association studies","volume":"44","author":"A Califano","year":"2012","journal-title":"Nat Genet"},{"issue":"6","key":"ref123","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/ng.3259","article-title":"Understanding multicellular function and disease with human tissue-specific networks","volume":"47","author":"CS Greene","year":"2015","journal-title":"Nat Genet"},{"issue":"4","key":"ref124","doi-asserted-by":"crossref","first-page":"045004","DOI":"10.1088\/1478-3975\/10\/4\/045004","article-title":"The spatial structure of cell signaling systems","volume":"10","author":"R Nussinov","year":"2013","journal-title":"Phys Biol"},{"issue":"38","key":"ref125","doi-asserted-by":"crossref","first-page":"13950","DOI":"10.1073\/pnas.0606312103","article-title":"Molecular switch for alternative conformations of the HIV-1 V3 region: implications for phenotype conversion","volume":"103","author":"O Rosen","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7159","key":"ref126","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/nature06108","article-title":"The structural basis of yeast prion strain variants","volume":"449","author":"BH Toyama","year":"2007","journal-title":"Nature"},{"issue":"1","key":"ref127","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12915-018-0524-5","article-title":"Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography","volume":"16","author":"JL Olmos Jr.","year":"2018","journal-title":"BMC Biol"},{"issue":"6214","key":"ref128","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1126\/science.1259357","article-title":"Time-resolved serial crystallography captures high-resolution intermediates of photoactive yellow protein","volume":"346","author":"J Tenboer","year":"2014","journal-title":"Science"},{"issue":"Pt 12","key":"ref129","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1107\/S0907444913025997","article-title":"Protein energy landscapes determined by five-dimensional crystallography","volume":"69","author":"M Schmidt","year":"2013","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"issue":"Pt 7","key":"ref130","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1107\/S0907444906017318","article-title":"Time-dependent atomic coordinates for the dissociation of carbon monoxide from myoglobin","volume":"62","author":"Aranda Rt","year":"2006","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/978-1-4939-7000-1_11","article-title":"Time-Resolved Macromolecular Crystallography at Modern X-Ray Sources","volume":"1607","author":"M Schmidt","year":"2017","journal-title":"Methods Mol Biol"},{"issue":"Pt 7","key":"ref132","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1107\/S2053230X15009061","article-title":"Towards time-resolved serial crystallography in a microfluidic device","volume":"71","author":"AS Pawate","year":"2015","journal-title":"Acta Crystallogr F Struct Biol Commun"},{"issue":"1647","key":"ref133","doi-asserted-by":"crossref","first-page":"20130568","DOI":"10.1098\/rstb.2013.0568","article-title":"Time-resolved crystallography and protein design: signalling photoreceptors and optogenetics","volume":"369","author":"K Moffat","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"1","key":"ref134","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/s12915-018-0533-4","article-title":"Entering an era of dynamic structural biology","volume":"16","author":"AM Orville","year":"2018","journal-title":"BMC Biol"},{"key":"ref135","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.sbi.2018.01.009","article-title":"Bringing diffuse X-ray scattering into focus","volume":"50","author":"ME Wall","year":"2018","journal-title":"Curr Opin Struct Biol"},{"key":"ref136","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/978-1-4939-7759-8_4","article-title":"Time-Resolved Cryo-electron Microscopy Using a Microfluidic Chip","volume":"1764","author":"S Kaledhonkar","year":"2018","journal-title":"Methods Mol Biol"},{"key":"ref137","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ymeth.2017.11.007","article-title":"Unraveling co-translational protein folding: Concepts and 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Ignatov","year":"2018","journal-title":"J Mol Biol"},{"issue":"22","key":"ref141","doi-asserted-by":"crossref","first-page":"5809","DOI":"10.1021\/acs.jpcb.8b02297","article-title":"Transition-State Ensembles Navigate the Pathways of Enzyme Catalysis","volume":"122","author":"MJ Mickert","year":"2018","journal-title":"J Phys Chem B"},{"issue":"12","key":"ref142","doi-asserted-by":"crossref","first-page":"8524","DOI":"10.1021\/acscatal.7b02954","article-title":"Role of Conformational Dynamics in the Evolution of Retro-Aldolase Activity","volume":"7","author":"A Romero-Rivera","year":"2017","journal-title":"ACS Catal"},{"issue":"7","key":"ref143","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.str.2016.05.012","article-title":"The Gearbox of the Bacterial Flagellar Motor Switch","volume":"24","author":"A Pandini","year":"2016","journal-title":"Structure"},{"issue":"44","key":"ref144","doi-asserted-by":"crossref","first-page":"13567","DOI":"10.1073\/pnas.1508584112","article-title":"From residue coevolution to protein conformational ensembles and functional dynamics","volume":"112","author":"L Sutto","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref145","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/j.ympev.2018.06.033","article-title":"How is structural divergence related to evolutionary information?","volume":"127","author":"DJ Zea","year":"2018","journal-title":"Mol Phylogenet Evol"},{"issue":"1","key":"ref146","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12859-018-2044-2","article-title":"Large scale analysis of protein conformational transitions from aqueous to non-aqueous media","volume":"19","author":"AJV Rueda","year":"2018","journal-title":"BMC 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