{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T22:26:07Z","timestamp":1776378367550,"version":"3.51.2"},"reference-count":124,"publisher":"Public Library of Science (PLoS)","issue":"4","content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000349","type":"journal-article","created":{"date-parts":[[2009,4,16]],"date-time":"2009-04-16T21:43:57Z","timestamp":1239918237000},"page":"e1000349","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":60,"title":["Inferring Stabilizing Mutations from Protein Phylogenies: Application to Influenza Hemagglutinin"],"prefix":"10.1371","volume":"5","author":[{"given":"Jesse D.","family":"Bloom","sequence":"first","affiliation":[]},{"given":"Matthew J.","family":"Glassman","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2009,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0959-440X(95)80081-6","article-title":"Knowledge-based potentials for proteins.","volume":"5","author":"MF Sippl","year":"1995","journal-title":"Curr Opin Struct Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/protein\/12.7.549","article-title":"Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations.","volume":"12","author":"MM Gromiha","year":"1999","journal-title":"Protein Eng"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/protein\/13.12.849","article-title":"PoPMuSiC, an algorithm for predicting protein mutant stability changes. application to prion proteins.","volume":"13","author":"D Gilis","year":"2000","journal-title":"Protein Eng"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/S0022-2836(02)00442-4","article-title":"Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations.","volume":"320","author":"R Guerois","year":"2002","journal-title":"J Mol Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0022-2836(02)00813-6","article-title":"Evaluation of structural and evolutionary contributions to deleterious protein mutation prediction.","volume":"322","author":"CT Saunders","year":"2002","journal-title":"J Mol Biol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1110\/ps.0217002","article-title":"Distance-scaled, finite ideal-gas reference state improves structure-derived potentials of mean force for structure selection and stability prediction.","volume":"11","author":"H Zhou","year":"2002","journal-title":"Protein Sci"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"W306","DOI":"10.1093\/nar\/gki375","article-title":"I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure.","volume":"33","author":"E Capriotti","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"W239","DOI":"10.1093\/nar\/gkl190","article-title":"CUPSAT: prediction of protein stability upon point mutations.","volume":"34","author":"V Parthiban","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1006\/jmbi.1994.1434","article-title":"Sequence statistics reliably predict stabilizing mutations in a protein domain.","volume":"240","author":"B Steipe","year":"1994","journal-title":"J Mol Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"16172","DOI":"10.1021\/bi981788p","article-title":"Mutagenesis of a buried polar interaction in an SH3 domain: sequence conservation provides the best prediction of stability effects.","volume":"37","author":"KL Maxwell","year":"1998","journal-title":"Biochemistry"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/protein\/15.5.403","article-title":"The consensus concept for thermostability engineering of proteins: further proof of concept.","volume":"15","author":"M Lehmann","year":"2002","journal-title":"Protein Eng Des Sel"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/protein\/gzh091","article-title":"Construction of stabilized proteins by combinatorial consensus mutagenesis.","volume":"17","author":"N Amin","year":"2004","journal-title":"Protein Eng Des Sel"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S0076-6879(04)88016-9","article-title":"Consensus-based engineering of protein stability: from intrabodies to thermostable enzymes.","volume":"388","author":"B Steipe","year":"2004","journal-title":"Methods Enzymol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.jmb.2003.12.048","article-title":"Relation between protein stability, evolution and structure as probed by carboxylic acid mutations.","volume":"336","author":"R Godoy-Ruiz","year":"2004","journal-title":"J Mol Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/protein\/gzl006","article-title":"Improved mutants from directed evolution are biased to orthologous substitutions.","volume":"19","author":"JR Cochran","year":"2006","journal-title":"Protein Eng Des Sel"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.jmb.2006.07.065","article-title":"Natural selection for kinetic stability is a likely origin of correlations between mutational effects on protein energetics and frequencies of amino acid occurrences in sequence alignments.","volume":"362","author":"R Godoy-Ruiz","year":"2006","journal-title":"J Mol Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/protein\/gzl056","article-title":"The creation of a novel fluorescent protein guided by consensus engineering.","volume":"20","author":"M Dai","year":"2007","journal-title":"Protein Eng Des Sel"},{"key":"ref18","article-title":"Inferring Phylogenies","author":"J Felsenstein","year":"2004"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1093\/oxfordjournals.molbev.a025627","article-title":"Combining protein evolution and secondary structure.","volume":"13","author":"JL Thorne","year":"1996","journal-title":"Mol Biol Evol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1093\/genetics\/149.1.445","article-title":"Assessing the impact of secondary structure and solvent accessibility on protein evolution.","volume":"149","author":"N Goldman","year":"1998","journal-title":"Genetics"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/molbev\/msh112","article-title":"A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process.","volume":"21","author":"N Lartillot","year":"2004","journal-title":"Mol Biol Evol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/molbev\/msj048","article-title":"Estimation of amino acid residue substitution rates at local spatial regions and application in protein function inference: a Bayesian Monte Carlo approach.","volume":"23","author":"YY Tseng","year":"2006","journal-title":"Mol Biol Evol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/1471-2105-7-148","article-title":"Identification of physicochemical selective pressure on protein encoding nucleotide sequences.","volume":"7","author":"WSW Wong","year":"2006","journal-title":"BMC Bioinformatics"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/molbev\/msm097","article-title":"Quantifying the impact of protein tertiary structure on molecular evolution.","volume":"24","author":"SC Choi","year":"2007","journal-title":"Mol Biol Evol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/(SICI)1097-0134(19980815)32:3<289::AID-PROT4>3.0.CO;2-D","article-title":"Models of natural mutations including site heterogeneity.","volume":"32","author":"JM Koshi","year":"1998","journal-title":"Proteins"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1093\/oxfordjournals.molbev.a003857","article-title":"Structural constraints and emergence of sequence patterns in protein evolution.","volume":"18","author":"G Parisi","year":"2001","journal-title":"Mol Biol Evol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/oxfordjournals.molbev.a004089","article-title":"Site-specific amino acid replacement matrices from structurally constrained protein evolution simulations.","volume":"19","author":"MS Fornasari","year":"2002","journal-title":"Mol Biol Evol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1471-2148-6-43","article-title":"A protein evolution model with independent sites that reproduces site-specific amino acid distributions from the protein data bank.","volume":"6","author":"U Bastolla","year":"2006","journal-title":"BMC Evol Biol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1002\/prot.10016","article-title":"Why are proteins marginally stable?","volume":"46","author":"DM Taverna","year":"2002","journal-title":"Proteins"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1006\/jmbi.2001.5226","article-title":"Why are proteins so robust to site mutations?","volume":"315","author":"DM Taverna","year":"2002","journal-title":"J Mol Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1534\/genetics.106.061754","article-title":"Thermodynamics of neutral protein evolution.","volume":"175","author":"JD Bloom","year":"2007","journal-title":"Genetics"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"16152","DOI":"10.1073\/pnas.0705366104","article-title":"Protein stability imposes limits on organism complexity and speed of molecular evolution.","volume":"104","author":"KB Zeldovich","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1002\/jmr.747","article-title":"Showing your ID: intrinsic disorder as an ID for recognition, regulation and cell signaling.","volume":"18","author":"VN Uversky","year":"2005","journal-title":"J Mol Recognit"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/415343a","article-title":"Energetic landscape of <italic>\u03b1<\/italic>-lytic protease optimizes longevity through kinetic stability.","volume":"415","author":"SS Jaswal","year":"2002","journal-title":"Nature"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1073\/pnas.0510941103","article-title":"Solution structure of p53 core domain: structural basis for its instability.","volume":"103","author":"MP Canadillas","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1093\/genetics\/110.4.539","article-title":"Genetic analysis of staphylococcal nuclease: identification of three intragenic \u201cglobal\u201d suppressors of nuclease-minus mutations.","volume":"110","author":"D Shortle","year":"1985","journal-title":"Genetics"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"8829","DOI":"10.1073\/pnas.83.23.8829","article-title":"Bacteriophage <italic>\u03bb cro<\/italic> mutations: effects on activity and intracellular degradation.","volume":"83","author":"AA Pakula","year":"1986","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/340397a0","article-title":"Complete mutagenesis of the HIV-1 protease.","volume":"340","author":"DD Loeb","year":"1989","journal-title":"Nature"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.jmb.2006.08.020","article-title":"Point mutations in protein globular domains: contributions from function, stability, and misfolding.","volume":"363","author":"IE Sanchez","year":"2006","journal-title":"J Mol Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/emboj\/19.7.1441","article-title":"Mutational analysis of the propensity for amyloid formation by a globular protein.","volume":"19","author":"F Chiti","year":"2000","journal-title":"EMBO J"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1006\/jmbi.2000.3514","article-title":"Nature disfavors sequences of alternating polar and nonpolar amino acids: implications for amyloidogenesis.","volume":"296","author":"BM Broome","year":"2000","journal-title":"J Mol Biol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semcdb.2003.12.008","article-title":"Principles of protein folding, misfolding, and aggregation.","volume":"15","author":"CM Dobson","year":"2004","journal-title":"Semin Cell Dev Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cell.2008.05.042","article-title":"Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution.","volume":"134","author":"DA Drummond","year":"2008","journal-title":"Cell"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/0014-5793(92)80894-M","article-title":"Amino acid substitutions influencing intracellular protein folding pathways.","volume":"307","author":"A Mitraki","year":"1992","journal-title":"FEBS Lett"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/(SICI)1097-0134(20000701)40:1<58::AID-PROT80>3.0.CO;2-M","article-title":"Lower kinetic limit to protein thermal stability: a proposal regarding protein stability <italic>in vivo<\/italic> and its relation with misfolding diseases.","volume":"40","author":"IMP del Pino","year":"2000","journal-title":"Proteins"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1073\/pnas.97.4.1525","article-title":"Transition-state structure as a unifying basis in protein-folding mechanisms: contact order, chain topology, stabiity, and the extended nucleus mechanism.","volume":"97","author":"AR Fersht","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/83003","article-title":"The roles of stability and contact order in determining protein folding rates.","volume":"8","author":"AR Dinner","year":"2001","journal-title":"Nat Struct Biol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1006\/jmbi.2001.4968","article-title":"On the relationship between protein stability and folding kinetics: a comparative study of the N-terminal domains of RNase HI, <italic>E. coli and Bacillus stearothermophilus<\/italic> L9.","volume":"312","author":"S Sato","year":"2001","journal-title":"J Mol Biol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1006\/bbrc.2002.6526","article-title":"Linear correlation between thermal stability and folding kinetics of lysozyme.","volume":"291","author":"A Cao","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"R75","DOI":"10.1186\/gb-2005-6-9-r75","article-title":"Evidence for selection on synonymous mutations affecting stability of mrna secondary structure in mammals.","volume":"6","author":"JV Chamary","year":"2005","journal-title":"Genome Biol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1093\/genetics\/164.4.1291","article-title":"Translational selection and yeast proteome evolution.","volume":"164","author":"H Akashi","year":"2003","journal-title":"Genetics"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1093\/molbev\/msh004","article-title":"An analysis of determinants of amino acids substitution rates in bacterial proteins.","volume":"21","author":"EPC Rocha","year":"2004","journal-title":"Mol Biol Evol"},{"key":"ref53","article-title":"Structure and Mechanism in Protein Science","author":"AR Fersht","year":"1999"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"12706","DOI":"10.1021\/bi00165a023","article-title":"Influence of transition rates and scan rate and kinetic simulations of differential scanning calorimetry profiles of reversible and irreversible protein denaturation.","volume":"31","author":"JR Lepock","year":"1992","journal-title":"Biochemistry"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nmeth740","article-title":"Pulse proteolysis: a simple method for quantitative determination of protein stability and ligand binding.","volume":"2","author":"C Park","year":"2005","journal-title":"Nat Methods"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1073\/pnas.0406744102","article-title":"Thermodynamic prediction of protein neutrality.","volume":"102","author":"JD Bloom","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1073\/pnas.0510098103","article-title":"Protein stability promotes evolvability.","volume":"103","author":"JD Bloom","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/prot.21227","article-title":"Relative tolerance of mesostable and thermostable protein homologs to extensive mutation.","volume":"66","author":"W Besenmatter","year":"2007","journal-title":"Proteins"},{"key":"ref59","first-page":"725","article-title":"A codon-based model of nucleotide substitution probabilities for protein-coding DNA sequences.","volume":"11","author":"N Goldman","year":"1994","journal-title":"Mol Biol Evol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"8509","DOI":"10.1021\/bi00489a001","article-title":"Additivity of mutational effects in proteins.","volume":"29","author":"JA Wells","year":"1990","journal-title":"Biochemistry"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"7205","DOI":"10.1021\/bi00444a012","article-title":"Large increases in general stability for subtilisin BPN&apos; through incremental changes in free energy of unfolding.","volume":"28","author":"MW Pantoliano","year":"1989","journal-title":"Biochemistry"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/protein\/8.10.1017","article-title":"Enhancement of protein stability by the combination of point mutations in T4 lysozyme is additive.","volume":"8","author":"XJ Zhang","year":"1995","journal-title":"Protein Eng"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"8367","DOI":"10.1073\/pnas.90.18.8367","article-title":"Engineering multiple properties of a protein by combinatorial mutagenesis.","volume":"90","author":"WS Sandberg","year":"1993","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/S0022-2836(03)00357-7","article-title":"Systematic variation of amino acid substitutions for stringent assessment of pairwise covariation.","volume":"328","author":"S Govindarajan","year":"2003","journal-title":"J Mol Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1006\/jmbi.1993.1508","article-title":"Step-wise mutation of barnase to binase: a procedure for engineering increased stability of proteins and an experimental analysis of the evolution of protein stability.","volume":"233","author":"L Serrano","year":"1993","journal-title":"J Mol Biol"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1103\/PhysRevLett.79.765","article-title":"Nature of driving force for protein folding: a result from analyzing the statistical potential.","volume":"79","author":"H Li","year":"1997","journal-title":"Phys Rev Lett"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"9716","DOI":"10.1073\/pnas.96.17.9716","article-title":"Neutral evolution of mutational robustness.","volume":"96","author":"E van Nimwegen","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1741-7007-5-29","article-title":"Evolution favors protein mutational robustness in sufficiently large populations..","volume":"5","author":"JD Bloom","year":"2007","journal-title":"BMC Biol"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1126\/science.1065889","article-title":"Bayesian inference of phylogeny and its impact on evolutionary biology.","volume":"294","author":"JP Huelsenbeck","year":"2001","journal-title":"Science"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1080\/10635150290102366","article-title":"Potential applications and pitfalls of Bayesian inference of phylogeny.","volume":"51","author":"JP Huelsenbeck","year":"2002","journal-title":"Syst Biol"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/bioinformatics\/btg180","article-title":"MrBayes 3: Bayesian phylogenetic inference under mixed models.","volume":"19","author":"F Ronquist","year":"2003","journal-title":"Bioinformatics"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"240","DOI":"10.2307\/2412304","article-title":"Maximum likelihood and minimum-step methods for estimating evolutionary trees from data on discrete characters.","volume":"22","author":"J Felsenstein","year":"1973","journal-title":"Syst Zool"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1007\/BF01734359","article-title":"Evolutionary trees from DNA sequences: a maximum likelihood approach.","volume":"17","author":"J Felsenstein","year":"1981","journal-title":"J Mol Evol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"D204","DOI":"10.1093\/nar\/gkj103","article-title":"ProTherm and ProNIT: thermodynamic databases for proteins and protein-nucleic acid interactions.","volume":"34","author":"MD Kumar","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"ref75","article-title":"PHYLIP (Phylogeny Inference Package) version 3.67. Distributed by the author","author":"J Felsenstein","year":"2007"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1101\/gr.2821705","article-title":"PROBCONS: probabilistic consistency-based multiple sequence alignment.","volume":"15","author":"CB Do","year":"2005","journal-title":"Genome Res"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput.","volume":"32","author":"RC Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"11887","DOI":"10.1128\/JVI.01414-06","article-title":"Comparison of avian and human influenza A viruses reveals a mutational bias on the viral genomes.","volume":"80","author":"R Rabadan","year":"2006","journal-title":"J Virol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"e22","DOI":"10.1371\/journal.pgen.0030022","article-title":"Transition-transversion bias is not universal: a counter example from grasshopper psuedogenes.","volume":"3","author":"I Keller","year":"2007","journal-title":"PLoS Genet"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1162\/089976602760805296","article-title":"On different facets of regularization theory.","volume":"14","author":"Z Chen","year":"2002","journal-title":"Neural Comput"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A simple method for displaying the hydropathic character of a protein.","volume":"157","author":"J Kyte","year":"1982","journal-title":"J Mol Biol"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"D120","DOI":"10.1093\/nar\/gkh082","article-title":"Protherm, version 4.0: thermodynamic database for proteins and mutants.","volume":"32","author":"KA Bava","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"D193","DOI":"10.1093\/nar\/gkl929","article-title":"The Universal Protein Resource (UniProt).","volume":"35","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0022-2836(02)00243-7","article-title":"Origins of the high stability of an <italic>in vitro<\/italic> selected coldshock protein.","volume":"318","author":"A Martin","year":"2002","journal-title":"J Mol Biol"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/75151","article-title":"Two exposed amino acid residues confer thermostability on a cold shock protein.","volume":"7","author":"D Perl","year":"2000","journal-title":"Nat Struct Biol"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.jmb.2004.04.011","article-title":"The folding transition state of the cold shock protein is strongly polarized.","volume":"339","author":"MM Garcia-Mira","year":"2004","journal-title":"J Mol Biol"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jmb.2005.02.014","article-title":"Stabilization of the cold shock protein CspB from <italic>Bacillus subtilis<\/italic> by evolutionary optimization of coulombic interactions.","volume":"347","author":"M Wunderlich","year":"2005","journal-title":"J Mol Biol"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1021\/bi982487i","article-title":"Microsecond folding of the cold shock protein measured by a pressure-jump technique.","volume":"38","author":"M Jacob","year":"1999","journal-title":"Biochemistry"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jmb.2006.11.061","article-title":"Role of the charge-charge interactions in defining stability and halophilicity of the CspB proteins.","volume":"366","author":"AV Gribenko","year":"2007","journal-title":"J Mol Biol"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"18686","DOI":"10.1074\/jbc.272.30.18686","article-title":"Conformational stabilities of <italic>Escherichia coli<\/italic> RNase HI variants with a series of amino acid substitutions at a cavity within the hydrophobic core.","volume":"272","author":"A Akasako","year":"1997","journal-title":"J Biol Chem"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"8115","DOI":"10.1021\/bi00025a018","article-title":"High resistance of <italic>Escherichia coli<\/italic> ribonuclease HI variant with quintiple thermostabilizing mutations to thermal denaturation, acid denaturation, and proteolytic degradation.","volume":"34","author":"A Akasako","year":"1995","journal-title":"Biochemistry"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"26904","DOI":"10.1016\/S0021-9258(18)47105-0","article-title":"A novel screening strategy for stabilization of <italic>Escherichia coli<\/italic> ribonuclease HI involving a screen for an intragenic suppressor of carboxyl-terminal deletions.","volume":"269","author":"M Haruki","year":"1994","journal-title":"J Biol Chem"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"7136","DOI":"10.1021\/bi00079a010","article-title":"Cooperative stabilization of <italic>Escherichia coli<\/italic> ribonuclease HI by insertion of Gly-80b and Gly-77\u2192Ala substitution.","volume":"32","author":"K Ishikawa","year":"1993","journal-title":"Biochemistry"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1021\/bi00075a009","article-title":"Stabilization of <italic>Escherichia coli<\/italic> ribonuclease HI by cavity-filling mutations within a hydrophobic core.","volume":"32","author":"K Ishikawa","year":"1993","journal-title":"Biochemistry"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"22014","DOI":"10.1016\/S0021-9258(18)41628-6","article-title":"Thermostabilization of <italic>Escherichia coli<\/italic> ribonuclease HI by replacing left-handed Lys95 with Gly or Asn.","volume":"267","author":"S Kimura","year":"1992","journal-title":"J Biol Chem"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1432-1033.1992.tb16932.x","article-title":"Effect of cavity-modulating mutations on the stability of <italic>Escherichia coli<\/italic> ribonuclease HI.","volume":"206","author":"S Kimura","year":"1992","journal-title":"Eur J Biochem"},{"key":"ref97","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1529\/biophysj.105.067025","article-title":"A stability pattern of hydrophobic mutations that reflects evolutionary structural optimization.","volume":"89","author":"R Godoy-Ruiz","year":"2005","journal-title":"Biophys J"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"11203","DOI":"10.1021\/bi00160a034","article-title":"The hydrophobic core of <italic>Escherichia coli<\/italic> thioredoxin shows a high tolerance to nonconservative single amino acid substitutions.","volume":"31","author":"HW Hellinga","year":"1992","journal-title":"Biochemistry"},{"key":"ref99","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/364164a0","article-title":"Universal nucleic acid-binding domain revealed by crystal structure of the <italic>B. subtilis<\/italic> major cold-shock protein.","volume":"364","author":"H Schindelin","year":"1993","journal-title":"Nature"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/0022-2836(92)90260-Q","article-title":"Structural details of ribonuclease H from <italic>Escherichia coli<\/italic> as refined to an atomic resolution.","volume":"223","author":"K Katayanagi","year":"1992","journal-title":"J Mol Biol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.02005-07","article-title":"The Influenza Virus Resource at the National Center for Biotechnology Information.","volume":"82","author":"Y Bao","year":"2008","journal-title":"J Virol"},{"key":"ref102","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nature06945","article-title":"The genomic and epidemiological dynamics of human influenza A virus.","volume":"453","author":"A Rambaut","year":"2008","journal-title":"Nature"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"e1000076","DOI":"10.1371\/journal.ppat.1000076","article-title":"The evolutionary genetics and emergence of avian influenza viruses in wild birds.","volume":"4","author":"VG Dugan","year":"2008","journal-title":"PLoS Pathog"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1099\/0022-1317-65-11-1889","article-title":"Physiological characterization of influenza virus temperature-sensitive mutants defective in the hemagglutinin gene.","volume":"65","author":"M Ueda","year":"1984","journal-title":"J Gen Virol"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/0042-6822(86)90454-X","article-title":"Identification of the defects in the hemagglutinin gene of two temperature-sensitive mutants of A\/WSN\/33 influenza virus.","volume":"154","author":"S Nakajima","year":"1986","journal-title":"Virology"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1111\/j.1348-0421.1995.tb03257.x","article-title":"Identification of the sites for suppressor mutations on the hemagglutinin molecule to temperature-sensitive phenotype of the influenza virus.","volume":"39","author":"N Tong","year":"1995","journal-title":"Microbiol Immunol"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1126\/science.1093155","article-title":"The structure and receptor binding properties of the 1918 influenza hemagglutinin.","volume":"303","author":"SJ Gamblin","year":"2004","journal-title":"Science"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1098\/rstb.2001.1001","article-title":"The predicted antigenicity of the haemagglutinin of the 1918 Spanish influenza pandemic suggests an avian origin.","volume":"356","author":"GG Brownlee","year":"2001","journal-title":"Philos Trans R Soc Lond B"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"6108","DOI":"10.1073\/pnas.100133697","article-title":"A DNA transfection system for generation of influenza A virus from eight plasmids.","volume":"97","author":"E Hoffmann","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"12809","DOI":"10.1073\/pnas.95.22.12809","article-title":"Directed evolution of a thermostable esterase.","volume":"95","author":"L Giver","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1093\/protein\/12.1.47","article-title":"Directed evolution converts subtilisin E into a functional equivalent of thermitase.","volume":"12","author":"H Zhao","year":"1999","journal-title":"Protein Eng"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1002\/1615-4169(200108)343:6\/7<607::AID-ADSC607>3.0.CO;2-M","article-title":"Rapid evolution of reversible denaturation and elevated melting temperature in a microbial haloalkane dehalogenase.","volume":"343","author":"KA Gray","year":"2001","journal-title":"Adv Synth Catal"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1128\/AEM.70.5.3041-3046.2004","article-title":"Enhancing the thermal tolerance and gastric performance of a microbial phytase for use as a phosphate-mobilizing monogastric-feed supplement.","volume":"70","author":"JB Garrett","year":"2004","journal-title":"Appl Environ Microbiol"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1128\/AEM.69.1.139-145.2002","article-title":"Thermostabilization of bacterial fructosyl-amino acid oxidase by directed evolution.","volume":"69","author":"R Sakaue","year":"2003","journal-title":"Appl Environ Microbiol"},{"key":"ref115","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1126\/science.181.4096.223","article-title":"Principles that govern the folding of protein chains.","volume":"181","author":"CB Anfinsen","year":"1973","journal-title":"Science"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1146\/annurev.biophys.28.1.319","article-title":"Membrane protein folding and stability: physical principles.","volume":"28","author":"SH White","year":"1999","journal-title":"Annu Rev Biophys Biomol Struct"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1006\/jmbi.1993.1294","article-title":"On the pH dependence of protein stability.","volume":"231","author":"AS Yang","year":"1993","journal-title":"J Mol Biol"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1006\/jmbi.1994.1258","article-title":"Structural origins of pH and ionic strength effects on protein stability acid denaturation of sperm whale myoglobin.","volume":"237","author":"AS Yang","year":"1994","journal-title":"J Mol Biol"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/S0959-440X(00)00172-X","article-title":"Macromolecular crowding: an important but neglected aspect of the intracellular environment.","volume":"11","author":"RJ Ellis","year":"2001","journal-title":"Curr Opin Struct Biol"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0300-9629(97)00004-2","article-title":"Thermophilic proteins: stability and function in aqueous and organic solvents.","volume":"118","author":"DA Cowan","year":"1997","journal-title":"Comp Biochem Physiol A Physiol"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nrg1838","article-title":"An integrated view of protein evolution.","volume":"7","author":"C Pal","year":"2006","journal-title":"Nat Rev Genet"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/molbev\/msj038","article-title":"A single determinant dominates the rate of yeast protein evolution.","volume":"23","author":"DA Drummond","year":"2006","journal-title":"Mol Biol Evol"},{"key":"ref123","doi-asserted-by":"crossref","first-page":"15G.1.1","DOI":"10.1002\/0471729256.mc15g01s3","article-title":"Influenza: propagation, quantification, and storage.","volume":"2006","author":"KJ Szretter","year":"2006","journal-title":"Curr Protoc Microbiol"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1743-422X-3-63","article-title":"New low-viscosity overlay medium for viral plaque assays.","volume":"3","author":"M Matrosovich","year":"2006","journal-title":"Virol J"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000349","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T06:05:33Z","timestamp":1633327533000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000349"}},"subtitle":[],"editor":[{"given":"Eugene I.","family":"Shakhnovich","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2009,4,17]]},"references-count":124,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2009,4,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000349","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,17]]}}}