High-quality thermodynamic data on the stability changes of proteins upon single-site mutations

We have set up and manually curated a dataset containing experimental information on the impact of amino acid substitutions in a protein on its thermal stability. It consists of a repository of experimentally measured melting temperatures (Tm) and their changes upon point mutations (ΔTm) for proteins having a well-resolved x-ray structure. This high-quality dataset is designed for being used for the training or benchmarking of in silico thermal stability prediction methods. It also reports other experimentally measured thermodynamic quantities when available, i.e., the folding enthalpy (ΔH) and heat capacity (ΔCP) of the wild type proteins and their changes upon mutations (ΔΔH and ΔΔCP), as well as the change in folding free energy (ΔΔG) at a reference temperature. These data are analyzed in view of improving our insights into the correlation between thermal and thermodynamic stabilities, the asymmetry between the number of stabilizing and destabilizing mutations, and the difference in stabilization poten...

[1]  S. Capasso,et al.  Thermodynamic analysis of the effect of selective monodeamidation at asparagine 67 in ribonuclease A , 1997, Protein science : a publication of the Protein Society.

[2]  H. Saito,et al.  Contributions of the N- and C-terminal helical segments to the lipid-free structure and lipid interaction of apolipoprotein A-I. , 2006, Biochemistry.

[3]  M Itaya,et al.  A novel strategy for stabilization of Escherichia coli ribonuclease HI involving a screen for an intragenic suppressor of carboxyl-terminal deletions. , 1994, The Journal of biological chemistry.

[4]  H. Mantsch,et al.  Structural and catalytic role of arginine 88 in Escherichia coli adenylate kinase as evidenced by chemical modification and site-directed mutagenesis. , 1989, The Journal of biological chemistry.

[5]  B. Matthews,et al.  Perturbation of Trp 138 in T4 lysozyme by mutations at Gln 105 used to correlate changes in structure, stability, solvation, and spectroscopic properties , 1993, Proteins.

[6]  A. Benito,et al.  Stabilization of human pancreatic ribonuclease through mutation at its N-terminal edge. , 2002, Protein engineering.

[7]  S. Bottomley,et al.  Probing the equilibrium denaturation of the serpin alpha(1)-antitrypsin with single tryptophan mutants; evidence for structure in the urea unfolded state. , 2001, Journal of molecular biology.

[8]  Michael Wunderlich,et al.  The correlation between protein stability and dipole moment: a critical test. , 2006, Protein engineering, design & selection : PEDS.

[9]  N. Nosworthy,et al.  Conformational stability changes of the amino terminal domain of enzyme I of the Escherichia coli phosphoenolpyruvate:sUgar phosphotransferase system produced by substituting alanine or glutamate for the active‐site histidine 189: Implications for phosphorylation effects , 2000, Protein science : a publication of the Protein Society.

[10]  Structure of a His170Tyr mutant of thermostable pNPPase from Geobacillus stearothermophilus. , 2014, Acta crystallographica. Section F, Structural biology communications.

[11]  Y. Yamagata,et al.  Role of amino acid residues in left‐handed helical conformation for the conformational stability of a protein , 2001, Proteins.

[12]  J. Whisstock,et al.  Probing the role of the F-helix in serpin stability through a single tryptophan substitution. , 2002, Biochemistry.

[13]  R. Raines,et al.  Structure and stability of the P93G variant of ribonuclease A , 1998, Protein science : a publication of the Protein Society.

[14]  W. Baase,et al.  Protein folding: assignment of the energetic changes of reversible chemical modifications to the folded or unfolded states. , 1992, Biochemistry.

[15]  C. Haynes,et al.  The role of a conserved tyrosine residue in high‐potential iron sulfur proteins , 1995, Protein science : a publication of the Protein Society.

[16]  Luis Serrano,et al.  A thermodynamic and kinetic analysis of the folding pathway of an SH3 domain entropically stabilised by a redesigned hydrophobic core. , 2003, Journal of molecular biology.

[17]  Bryan S. Der,et al.  Analysis of ligand binding to a ribose biosensor using site‐directed mutagenesis and fluorescence spectroscopy , 2007, Protein science : a publication of the Protein Society.

[18]  Y. Yamagata,et al.  A general rule for the relationship between hydrophobic effect and conformational stability of a protein: stability and structure of a series of hydrophobic mutants of human lysozyme. , 1998, Journal of molecular biology.

[19]  Y. Yamagata,et al.  Contribution of amino acid substitutions at two different interior positions to the conformational stability of human lysozyme. , 1999, Protein engineering.

[20]  R. Brzezinski,et al.  Thermal unfolding of chitosanase from Streptomyces sp. N174: role of tryptophan residues in the protein structure stabilization. , 1999, Biochimica et biophysica acta.

[21]  D. E. Anderson,et al.  pH-induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme. , 1990, Biochemistry.

[22]  M. Oobatake,et al.  Thermal Stability of Escherichia coli Ribonuclease HI and Its Active Site Mutants in the Presence and Absence of the Mg2+ Ion , 1996, The Journal of Biological Chemistry.

[23]  J. Sturtevant,et al.  Differential scanning calorimetric study of the thermal unfolding of mutant forms of phage T4 lysozyme. , 1992, Biochemistry.

[24]  Y. Igarashi,et al.  Thermodynamic characterization of variants of mesophilic cytochrome c and its thermophilic counterpart. , 2002, Protein engineering.

[25]  G. Haki,et al.  Developments in industrially important thermostable enzymes: a review. , 2003, Bioresource technology.

[26]  B. Matthews,et al.  A test of the "jigsaw puzzle" model for protein folding by multiple methionine substitutions within the core of T4 lysozyme. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[27]  K. Sode,et al.  Increasing the hydrophobic interaction between terminal W-motifs enhances the stability of Salmonella typhimurium sialidase. A general strategy for the stabilization of beta-propeller protein fold. , 2001, Protein engineering.

[28]  G. Brayer,et al.  Thermal stability of hydrophobic heme pocket variants of oxidized cytochrome c , 1999, Protein science : a publication of the Protein Society.

[29]  J. Hofrichter,et al.  Experimental tests of villin subdomain folding simulations. , 2003, Journal of molecular biology.

[30]  K. Kirschner,et al.  The hyperthermostable indoleglycerol phosphate synthase from Thermotoga maritima is destabilized by mutational disruption of two solvent-exposed salt bridges. , 1999, Journal of molecular biology.

[31]  F. Musayev,et al.  Significance of Local Electrostatic Interactions in Staphylococcal Nuclease Studied by Site-directed Mutagenesis* , 2001, The Journal of Biological Chemistry.

[32]  K. Mavromatis,et al.  Cold adaptation of a psychrophilic chitinase: a mutagenesis study. , 2003, Protein engineering.

[33]  P. Privalov,et al.  Thermodynamics of staphylococcal nuclease denaturation. II. The A‐state , 1994, Protein science : a publication of the Protein Society.

[34]  Axel T. Brünger,et al.  Amino-acid substitutions in a surface turn modulate protein stability , 1996, Nature Structural Biology.

[35]  Compensatory Stabilizing Role of Surface Mutations During the Directed Evolution of Dienelactone Hydrolase for Enhanced Activity , 2015, The Protein Journal.

[36]  Eun Jung Choi,et al.  Generation and analysis of proline mutants in protein G. , 2006, Protein engineering, design & selection : PEDS.

[37]  W. Stites,et al.  Chemically crosslinked protein dimers: Stability and denaturation effects , 1995, Protein science : a publication of the Protein Society.

[38]  J. Chen,et al.  Thermodynamic cycles as probes of structure in unfolded proteins. , 1996, Biochemistry.

[39]  Pengfei Zhou,et al.  Residue Asn277 Affects the Stability and Substrate Specificity of the SMG1 Lipase from Malassezia globosa , 2015, International journal of molecular sciences.

[40]  D. L. Veenstra,et al.  Stabilizing and destabilizing effects of placing beta-branched amino acids in protein alpha-helices. , 1994, Biochemistry.

[41]  A. Grinberg,et al.  Contribution of a salt bridge to the thermostability of adrenodoxin determined by site-directed mutagenesis. , 2001, Archives of biochemistry and biophysics.

[42]  Determination of alpha-helix propensity within the context of a folded protein. Sites 44 and 131 in bacteriophage T4 lysozyme. , 1993, Journal of molecular biology.

[43]  B. Matthews,et al.  Analysis of the effectiveness of proline substitutions and glycine replacements in increasing the stability of phage T4 lysozyme , 1992, Biopolymers.

[44]  J A Wozniak,et al.  Replacements of Pro86 in phage T4 lysozyme extend an alpha-helix but do not alter protein stability. , 1990, Science.

[45]  R. Kelley,et al.  Effect of residue 65 substitutions on thermal stability of tissue plasminogen activator kringle-2 domain. , 1989, Biochemistry.

[46]  Accommodation of amino acid insertions in an alpha-helix of T4 lysozyme. Structural and thermodynamic analysis. , 1994, Journal of molecular biology.

[47]  Akinori Sarai,et al.  ProTherm and ProNIT: thermodynamic databases for proteins and protein–nucleic acid interactions , 2005, Nucleic Acids Res..

[48]  J A Wozniak,et al.  Structural and thermodynamic analysis of the packing of two alpha-helices in bacteriophage T4 lysozyme. , 1991 .

[49]  R. Lewis,et al.  Probing the structural basis for the difference in thermostability displayed by family 10 xylanases. , 2006, Journal of molecular biology.

[50]  V. Lobachov,et al.  Key role of phenylalanine 20 in cytochrome c3: structure, stability, and function studies. , 1999, Biochemistry.

[51]  K. Gekko,et al.  Point mutations at glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function. , 1994, Journal of biochemistry.

[52]  C. Evrard,et al.  Histidine modification and mutagenesis point to the involvement of a large conformational change in the mechanism of action of phage lambda lysozyme , 1999, FEBS letters.

[53]  A. Fersht,et al.  Effect of cavity-creating mutations in the hydrophobic core of chymotrypsin inhibitor 2. , 1993, Biochemistry.

[54]  Jan H. Jensen,et al.  Effect of mutations on the thermostability of Aspergillus aculeatus β-1,4-galactanase , 2015, Computational and structural biotechnology journal.

[55]  Tatzuo Ueki,et al.  Minimization of cavity size ensures protein stability and folding: structures of Phe46-replaced bovine pancreatic RNase A. , 2003, Biochemistry.

[56]  R. Bernhardt,et al.  The Role of Threonine 54 in Adrenodoxin for the Properties of Its Iron-Sulfur Cluster and Its Electron Transfer Function (*) , 1995, The Journal of Biological Chemistry.

[57]  Kevin L. Shaw,et al.  Increasing protein stability by altering long‐range coulombic interactions , 1999, Protein science : a publication of the Protein Society.

[58]  D. Atkinson,et al.  Lipid-free structure and stability of apolipoprotein A-I: probing the central region by mutation. , 2002, Biochemistry.

[59]  K. Wüthrich,et al.  Designed replacement of an internal hydration water molecule in BPTI: structural and functional implications of a glycine-to-serine mutation. , 1993, Biochemistry.

[60]  A. Clark,et al.  Thermodynamics of core hydrophobicity and packing in the hyperthermophile proteins Sac7d and Sso7d. , 2004, Biochemistry.

[61]  K. Teuchner,et al.  Unfolding and conformational studies on bovine adrenodoxin probed by engineered intrinsic tryptophan fluorescence. , 2002, Biochemistry.

[62]  J. Sturtevant,et al.  Thermal unfolding of staphylococcal nuclease and several mutant forms thereof studied by differential scanning calorimetry , 1993, Protein science : a publication of the Protein Society.

[63]  G. Feller,et al.  Structural Determinants of Cold Adaptation and Stability in a Large Protein* , 2001, The Journal of Biological Chemistry.

[64]  B. Matthews,et al.  Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme. , 1991, Biochemistry.

[65]  G. Rose,et al.  Effects of alanine substitutions in α‐helices of sperm whale myoglobin on protein stability , 1993, Protein science : a publication of the Protein Society.

[66]  A. G. Day,et al.  Comparison of family 12 glycoside hydrolases and recruited substitutions important for thermal stability , 2003, Protein science : a publication of the Protein Society.

[67]  B. Shoichet,et al.  Functional analyses of AmpC β‐lactamase through differential stability , 1999 .

[68]  P. Wolynes,et al.  Spin glasses and the statistical mechanics of protein folding. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[69]  Y. H. Wang,et al.  Importance of a conserved phenylalanine-35 of cytochrome b5 to the protein's stability and redox potential. , 1997, Protein engineering.

[70]  F. Castellino,et al.  Involvement of tyrosine-76 of the kringle 2 domain of tissue-type plasminogen activator in its thermal stability and its omega-amino acid ligand binding site. , 1994, Biochemistry.

[71]  S. Anderson,et al.  Alanine Point-Mutations in the Reactive Region of Bovine Pancreatic Trypsin Inhibitor: Effects on the Kinetics and Thermodynamics of Binding to β-Trypsin and α-Chymotrypsin† , 1996 .

[72]  R. Raines,et al.  Genetic selection reveals the role of a buried, conserved polar residue , 2007, Protein science : a publication of the Protein Society.

[73]  Kevin L. Shaw,et al.  Contribution of active site residues to the activity and thermal stability of ribonuclease Sa , 2003, Protein science : a publication of the Protein Society.

[74]  A. Fersht,et al.  Contribution of a proline residue and a salt bridge to the stability of a type I reverse turn in chymotrypsin inhibitor-2. , 1994, Protein engineering.

[75]  Thermal stability determinants of chicken egg‐white lysozyme core mutants: Hydrophobicity, packing volume, and conserved buried water molecules , 1994, Protein science : a publication of the Protein Society.

[76]  R. Boom,et al.  Thermozymes and their applications , 2001, Applied biochemistry and biotechnology.

[77]  E. Triphosphat,et al.  FEBS Letters , 1987, FEBS Letters.

[78]  L. J. Perry,et al.  Disulfide bonds and thermal stability in T4 lysozyme. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[79]  T. Poulos,et al.  Proteases of enhanced stability: Characteization of a thermostable variant of subtilisin , 1986, Proteins.

[80]  Motonori Ota,et al.  A hyperthermophilic protein acquires function at the cost of stability. , 2006, Biochemistry.

[81]  D E Tronrud,et al.  Contributions of left-handed helical residues to the structure and stability of bacteriophage T4 lysozyme. , 1990, Journal of molecular biology.

[82]  R. Bauerle,et al.  Site-directed mutagenesis of the alpha subunit of tryptophan synthase from Salmonella typhimurium. , 1988, Biochemical and biophysical research communications.

[83]  Y. Yamagata,et al.  Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six tyrosine --> phenylalanine mutants. , 1998, Biochemistry.

[84]  B. Matthews,et al.  Multiple alanine replacements within α‐helix 126–134 of T4 lysozyme have independent, additive effects on both structure and stability , 1991, Protein science : a publication of the Protein Society.

[85]  W. Pfeil,et al.  Conformational stability of adrenodoxin mutant proteins , 1996, Protein science : a publication of the Protein Society.

[86]  K. Brew,et al.  Role of conserved residues in structure and stability: Tryptophans of human serum retinol‐binding protein, a model for the lipocalin superfamily , 2001, Protein Science.

[87]  Y. Yamagata,et al.  Contribution of intra- and intermolecular hydrogen bonds to the conformational stability of human lysozyme(,). , 1999, Biochemistry.

[88]  A. Fersht,et al.  Mutational analysis of the N-capping box of the α-helix of chymotrypsin inhibitor 2 , 1994 .

[89]  M Ikehara,et al.  Effect of cavity-modulating mutations on the stability of Escherichia coli ribonuclease HI. , 1992, European journal of biochemistry.

[90]  R. W. Peterson,et al.  A partially buried site in homologous HPr proteins is not optimized for stability. , 2002, Journal of molecular biology.

[91]  B K Shoichet,et al.  A relationship between protein stability and protein function. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[92]  B K Shoichet,et al.  Enhancement of protein stability by the combination of point mutations in T4 lysozyme is additive. , 1995, Protein engineering.

[93]  R. Huber,et al.  Thermodynamic stability of annexin V E17G: equilibrium parameters from an irreversible unfolding reaction. , 1997, Biochemistry.

[94]  W. Stites,et al.  The M32L substitution of staphylococcal nuclease: disagreement between theoretical prediction and experimental protein stability. , 1996, Journal of Molecular Biology.

[95]  A. Fersht,et al.  Extrapolation to water of kinetic and equilibrium data for the unfolding of barnase in urea solutions. , 1994, Protein engineering.

[96]  E. J. Loveridge,et al.  Thermal Adaptation of Dihydrofolate Reductase from the Moderate Thermophile Geobacillus stearothermophilus , 2014, Biochemistry.

[97]  S. Spragg.  Biophysical chemistry , 1979, Nature.

[98]  S. L. Mayo,et al.  Polar residues in the protein core of Escherichia coli thioredoxin are important for fold specificity. , 2001, Biochemistry.

[99]  M. Oobatake,et al.  High resistance of Escherichia coli ribonuclease HI variant with quintuple thermostabilizing mutations to thermal denaturation, acid denaturation, and proteolytic degradation. , 1995, Biochemistry.

[100]  G. Brayer,et al.  Enhanced thermodynamic stabilities of yeast iso-1-cytochromes c with amino acid replacements at positions 52 and 102. , 1991, The Journal of biological chemistry.

[101]  S Kanaya,et al.  Thermostabilization of Escherichia coli ribonuclease HI by replacing left-handed helical Lys95 with Gly or Asn. , 1992, The Journal of biological chemistry.

[102]  S. Mazumdar,et al.  Role of threonine 101 on the stability of the heme active site of cytochrome P450cam: multiwavelength circular dichroism studies. , 2006, Biochemistry.

[103]  A. Sarai,et al.  Shape and energetics of a cavity in c-Myb probed by natural and non-natural amino acid mutations. , 1999, Journal of molecular biology.

[104]  Y. Yamagata,et al.  Positive Contribution of Hydration Structure on the Surface of Human Lysozyme to the Conformational Stability* , 2002, The Journal of Biological Chemistry.

[105]  J. Lehoux,et al.  Quantitative fluorometric analysis of the protective effect of chitosan on thermal unfolding of catalytically active native and genetically-engineered chitosanases. , 2007, Biochimica et biophysica acta.

[106]  Shin Kawano,et al.  Further enhancement of the thermostability of Hydrogenobacter thermophilus cytochrome c552. , 2006, Biochemistry.

[107]  B. Matthews,et al.  Similar hydrophobic replacements of Leu99 and Phe153 within the core of T4 lysozyme have different structural and thermodynamic consequences. , 1993, Journal of molecular biology.

[108]  L. Christophorou.  Science , 2018, Emerging Dynamics: Science, Energy, Society and Values.

[109]  A. Kidera,et al.  Atomically detailed description of the unfolding of alpha-lactalbumin by the combined use of experiments and simulations. , 2005, Journal of molecular biology.

[110]  B. Matthews,et al.  Methionine and alanine substitutions show that the formation of wild-type-like structure in the carboxy-terminal domain of T4 lysozyme is a rate-limiting step in folding. , 1999, Biochemistry.

[111]  U. Sauer,et al.  Tolerance of T4 lysozyme to proline substitutions within the long interdomain alpha-helix illustrates the adaptability of proteins to potentially destabilizing lesions. , 1991, The Journal of biological chemistry.

[112]  Yuichi Koga,et al.  Hydrophobic effect on the stability and folding of a hyperthermophilic protein. , 2008, Journal of molecular biology.

[113]  D. Laurents,et al.  Increase of RNase a N-terminus polarity or C-terminus apolarity changes the two domains' propensity to swap and form the two dimeric conformers of the protein. , 2006, Biochemistry.

[114]  U. Sauer,et al.  Contributions of engineered surface salt bridges to the stability of T4 lysozyme determined by directed mutagenesis. , 1991, Biochemistry.

[115]  J. Schellman,et al.  Thermodynamic stability and point mutations of bacteriophage T4 lysozyme. , 1984, Journal of molecular biology.

[116]  Kevin L. Shaw,et al.  Asp79 makes a large, unfavorable contribution to the stability of RNase Sa. , 2005, Journal of molecular biology.

[117]  H. Nicholson,et al.  Folding kinetics of T4 lysozyme and nine mutants at 12 degrees C. , 1992, Biochemistry.

[118]  Javier Santos,et al.  Effects of Serine-to-Cysteine Mutations on β-Lactamase Folding , 2007 .

[119]  J. Kirsch,et al.  Design and structural analysis of an engineered thermostable chicken lysozyme , 1995, Protein science : a publication of the Protein Society.

[120]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[121]  M. Bycroft,et al.  Electrostatic interactions contribute to reduced heat capacity change of unfolding in a thermophilic ribosomal protein l30e. , 2005, Journal of molecular biology.

[122]  S. Betz,et al.  Introduction of a disulfide bond into cytochrome c stabilizes a compact denatured state. , 1992, Biochemistry.

[123]  D F Doyle,et al.  Protein thermal denaturation, side-chain models, and evolution: amino acid substitutions at a conserved helix-helix interface. , 1995, Biochemistry.

[124]  R. Raines,et al.  Conformational Stability Is a Determinant of Ribonuclease A Cytotoxicity* , 2000, The Journal of Biological Chemistry.

[125]  George I Makhatadze,et al.  Effects of charge-to-alanine substitutions on the stability of ribosomal protein L30e from Thermococcus celer. , 2005, Biochemistry.

[126]  B. Matthews,et al.  Folding and function of a T4 lysozyme containing 10 consecutive alanines illustrate the redundancy of information in an amino acid sequence. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[127]  Hein J. Wijma,et al.  Computational Library Design for Increasing Haloalkane Dehalogenase Stability , 2014, Chembiochem : a European journal of chemical biology.

[128]  M. Oobatake,et al.  Investigating the role of conserved residue Asp134 in Escherichia coli ribonuclease HI by site-directed random mutagenesis. , 1994, European journal of biochemistry.

[129]  A. Benito,et al.  Pressure- and temperature-induced unfolding studies: thermodynamics of core hydrophobicity and packing of ribonuclease A , 2006, Biological chemistry.

[130]  Y. Yamagata,et al.  Effect of foreign N-terminal residues on the conformational stability of human lysozyme. , 1999, European journal of biochemistry.

[131]  B. Matthews,et al.  Structural analysis of a non-contiguous second-site revertant in T4 lysozyme shows that increasing the rigidity of a protein can enhance its stability. , 1999, Journal of molecular biology.

[132]  S. Lowen.  The Biophysical Journal , 1960, Nature.

[133]  H. Scheraga,et al.  Local and long-range interactions in the thermal unfolding transition of bovine pancreatic ribonuclease A. , 2001, Biochemistry.

[134]  B. Matthews,et al.  A mutant T4 lysozyme (Val 131 → Ala) designed to increase thermostability by the reduction of strain within an α‐helix , 1990, Proteins.

[135]  B. Matthews,et al.  Energetic cost and structural consequences of burying a hydroxyl group within the core of a protein determined from Ala-->Ser and Val-->Thr substitutions in T4 lysozyme. , 1993, Biochemistry.

[136]  B. Matthews,et al.  Response of a protein structure to cavity-creating mutations and its relation to the hydrophobic effect. , 1992, Science.

[137]  Stephen L Mayo,et al.  Repacking the Core of T4 lysozyme by automated design. , 2003, Journal of molecular biology.

[138]  Y. Yamagata,et al.  Contribution of the hydrophobic effect to the stability of human lysozyme: calorimetric studies and X-ray structural analyses of the nine valine to alanine mutants. , 1997, Biochemistry.

[139]  M. Oobatake,et al.  pH-dependent thermostabilization of Escherichia coli ribonuclease HI by histidine to alanine substitutions. , 1993, Journal of biotechnology.

[140]  Stefan M. Larson,et al.  The relationship between conservation, thermodynamic stability, and function in the SH3 domain hydrophobic core. , 2003, Journal of molecular biology.

[141]  Shoeb Ahmad,et al.  Thermally denatured state determines refolding in lipase: Mutational analysis , 2009, Protein science : a publication of the Protein Society.

[142]  Ronen Marmorstein,et al.  Structure-based Design of p18INK4cProteins with Increased Thermodynamic Stability and Cell Cycle Inhibitory Activity* , 2002, The Journal of Biological Chemistry.

[143]  W. Windsor,et al.  Improving tolerance of Candida antarctica lipase B towards irreversible thermal inactivation through directed evolution. , 2003, Protein engineering.

[144]  B. Matthews,et al.  Alanine scanning mutagenesis of the alpha-helix 115-123 of phage T4 lysozyme: effects on structure, stability and the binding of solvent. , 1995, Journal of molecular biology.

[145]  Y. Yamagata,et al.  Contribution of salt bridges near the surface of a protein to the conformational stability. , 2000, Biochemistry.

[146]  J. Ladbury,et al.  Substitution of charged residues into the hydrophobic core of Escherichia coli thioredoxin results in a change in heat capacity of the native protein. , 1995, Biochemistry.

[147]  A. Fersht,et al.  Energetics of complementary side-chain packing in a protein hydrophobic core. , 1989, Biochemistry.

[148]  N. Kallenbach,et al.  Alpha-helix stability and the native state of myoglobin. , 1993, Biochemistry.

[149]  C. Pace,et al.  Buried, charged, non-ion-paired aspartic acid 76 contributes favorably to the conformational stability of ribonuclease T1. , 1999, Biochemistry.

[150]  A. Surolia,et al.  Thermodynamics of replacing an α‐helical Pro residue in the P40S mutant of Escherichia coli thioredoxin , 2008, Protein science : a publication of the Protein Society.

[151]  R. Raines,et al.  Contribution of a tyrosine side chain to ribonuclease A catalysis and stability–Contribution of Tyr 97 to RNase A catalysis and stability , 1996, Protein science : a publication of the Protein Society.

[152]  K. Hiraga,et al.  A Thermodynamic Analysis of Conformational Change Due to the α2β2 Complex Formation of Tryptophan Synthase , 1996 .

[153]  Y. Yamagata,et al.  Role of surface hydrophobic residues in the conformational stability of human lysozyme at three different positions. , 2000, Biochemistry.

[154]  L. Ellerby,et al.  The role of lysine-234 in beta-lactamase catalysis probed by site-directed mutagenesis. , 1990, Biochemistry.

[155]  A. Koide,et al.  Stabilization of a fibronectin type III domain by the removal of unfavorable electrostatic interactions on the protein surface. , 2001, Biochemistry.

[156]  R. L. Baldwin,et al.  Cis proline mutants of ribonuclease A. I. thermal stability , 1992, Protein science : a publication of the Protein Society.

[157]  K. Yutani,et al.  Role of conserved proline residues in stabilizing tryptophan synthase α subunit: Analysis by mutants with alanine or glycine , 1991, Proteins.

[158]  A. Shaw,et al.  The Humicola grisea Cel12A enzyme structure at 1.2 Å resolution and the impact of its free cysteine residues on thermal stability , 2003, Protein science : a publication of the Protein Society.

[159]  Marianne Rooman,et al.  Predicting protein thermal stability changes upon point mutations using statistical potentials: Introducing HoTMuSiC , 2016, Scientific Reports.

[160]  F. Sherman,et al.  Stabilizing amino acid replacements at position 52 in yeast iso-1-cytochrome c: in vivo and in vitro effects. , 1995, Biochemistry.

[161]  G. Barone,et al.  Differential scanning calorimetry study of the thermodynamic stability of some mutants of Sso7d from Sulfolobus solfataricus. , 1998, Biochemistry.

[162]  Y. H. Wang,et al.  The effect of mutation at valine-45 on the stability and redox potentials of trypsin-cleaved cytochrome b5. , 2000, Biophysical chemistry.

[163]  A. Chedad,et al.  Tryptophan to phenylalanine substitutions allow differentiation of short‐ and long‐range conformational changes during denaturation of goat α‐lactalbumin , 2005, Proteins.

[164]  K. Brew,et al.  Stability, activity and flexibility in α-lactalbumin , 1999 .

[165]  Zachary F. Burton,et al.  α/β Proteins , 2018 .

[166]  C. Matthews,et al.  Effect of single amino acid substitutions on the thermal stability of the alpha subunit of tryptophan synthase. , 1980, Biochemistry.

[167]  B. Matthews,et al.  The response of T4 lysozyme to large‐to‐small substitutions within the core and its relation to the hydrophobic effect , 1998, Protein science : a publication of the Protein Society.

[168]  C. Pace,et al.  Contribution of a conserved asparagine to the conformational stability of ribonucleases Sa, Ba, and T1. , 1998, Biochemistry.

[169]  Marianne Rooman,et al.  Symmetry principles in optimization problems: an application to protein stability prediction , 2015 .

[170]  L. Gregoret,et al.  Examination of the folding of E. coli CspA through tryptophan substitutions , 2001, Protein science : a publication of the Protein Society.

[171]  W. Stites,et al.  Thermal denaturations of staphylococcal nuclease wild-type and mutants monitored by fluorescence and circular dichroism are similar: lack of evidence for other than a two state thermal denaturation. , 2007, Biophysical chemistry.

[172]  B. Matthews,et al.  The introduction of strain and its effects on the structure and stability of T4 lysozyme. , 1999, Journal of molecular biology.

[173]  U. Arnold,et al.  Contribution of structural peculiarities of onconase to its high stability and folding kinetics. , 2006, Biochemistry.

[174]  Z. Xia,et al.  Effect of mutation at valine 61 on the three-dimensional structure, stability, and redox potential of cytochrome b5. , 1999, Biochemistry.

[175]  N. Xuong,et al.  An engineered disulfide bond in dihydrofolate reductase. , 1987, Biochemistry.

[176]  George I Makhatadze,et al.  Role of the charge-charge interactions in defining stability and halophilicity of the CspB proteins. , 2007, Journal of molecular biology.

[177]  M. Rooman,et al.  Stability strengths and weaknesses in protein structures detected by statistical potentials: Application to bovine seminal ribonuclease , 2016, Proteins.

[178]  A. Hinck,et al.  Coupling between local structure and global stability of a protein: mutants of staphylococcal nuclease. , 1990, Biochemistry.

[179]  H. Scheraga,et al.  Folding and unfolding kinetics of the proline-to-alanine mutants of bovine pancreatic ribonuclease A. , 1996, Biochemistry.

[180]  Philip Pjura,et al.  Development of an in vivo method to identify mutants of phage T4 lysozyme of enhanced thermostability , 1993, Protein science : a publication of the Protein Society.

[181]  J A Wozniak,et al.  Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability. , 1991, Journal of molecular biology.

[182]  D. Perl,et al.  Electrostatic stabilization of a thermophilic cold shock protein. , 2001, Journal of molecular biology.

[183]  K. Takano,et al.  Role of non‐glycine residues in left‐handed helical conformation for the conformational stability of human lysozyme , 2001, Proteins.

[184]  Y. Yamagata,et al.  Contribution of water molecules in the interior of a protein to the conformational stability. , 1998, Journal of molecular biology.

[185]  R. Kautz,et al.  Fluorescence and conformational stability studies of Staphylococcus nuclease and its mutants, including the less stable nuclease-concanavalin A hybrids. , 1991, Biochemistry.

[186]  A. Davidson,et al.  Mutagenesis of a buried polar interaction in an SH3 domain: sequence conservation provides the best prediction of stability effects. , 1998, Biochemistry.

[187]  K Morikawa,et al.  Cooperative stabilization of Escherichia coli ribonuclease HI by insertion of Gly-80b and Gly-77-->Ala substitution. , 1994, Biochemistry.

[188]  H. Mantsch,et al.  Structural and functional consequences of amino acid substitutions in the second conserved loop of Escherichia coli adenylate kinase. , 1991, The Journal of biological chemistry.

[189]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[190]  C James McKnight,et al.  The role of aromatic residues in the hydrophobic core of the villin headpiece subdomain , 2002, Protein science : a publication of the Protein Society.

[191]  C. Pace,et al.  The Contribution of Polar Group Burial to Protein Stability Is Strongly Context-dependent* , 2003, Journal of Biological Chemistry.

[192]  Brian W. Matthews,et al.  Hydrophobic stabilization in T4 lysozyme determined directly by multiple substitutions of Ile 3 , 1988, Nature.

[193]  M. Deardorff,et al.  Compromised Structure and Function of HDAC8 Mutants Identified in Cornelia de Lange Syndrome Spectrum Disorders , 2014, ACS chemical biology.

[194]  D. Raleigh,et al.  Multistate folding of the villin headpiece domain. , 2006, Journal of molecular biology.

[195]  Michael P. Byrne,et al.  Energetic contribution of side chain hydrogen bonding to the stability of staphylococcal nuclease. , 1995, Biochemistry.

[196]  D. LeMaster,et al.  Residue cluster additivity of thermodynamic stability in the hydrophobic core of mesophile vs. hyperthermophile rubredoxins. , 2007, Biophysical chemistry.

[197]  C. Pace,et al.  Conformational Stability and Activity of Ribonuclease T1 and Mutants , 1989 .

[198]  I. André,et al.  Probing impact of active site residue mutations on stability and activity of Neisseria polysaccharea amylosucrase , 2013, Protein science : a publication of the Protein Society.

[199]  J M Sturtevant,et al.  Sidechain interactions in parallel beta sheets: the energetics of cross-strand pairings. , 1999, Structure.

[200]  Study of cysteine residues in the alpha subunit of Escherichia coli tryptophan synthase. 1. Role in conformational stability. , 1996, Protein engineering.

[201]  D. E. Anderson,et al.  Hydrophobic core repacking and aromatic–aromatic interaction in the thermostable mutant of T4 lysozyme ser 117 → phe , 1993, Protein science : a publication of the Protein Society.

[202]  Brian W Matthews,et al.  A helix initiation signal in T4 lysozyme identified by polyalanine mutagenesis. , 1995, Biophysical chemistry.

[203]  J. Macdonald,et al.  Structural analysis of thermostabilizing mutations of cocaine esterase. , 2010, Protein engineering, design & selection : PEDS.

[204]  H. Kamikubo,et al.  Elucidation of information encoded in tryptophan 140 of staphylococcal nuclease , 2004, Proteins.

[205]  R. Wetzel,et al.  Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency. , 2015, Biochimica et biophysica acta.

[206]  B. Tidor,et al.  Surface salt bridges, double-mutant cycles, and protein stability: an experimental and computational analysis of the interaction of the Asp 23 side chain with the N-terminus of the N-terminal domain of the ribosomal protein l9. , 2003, Biochemistry.

[207]  D. Yannoukakos,et al.  Thermal unfolding of human BRCA1 BRCT-domain variants. , 2007, Biochimica et biophysica acta.

[208]  K Nishikawa,et al.  Experimental verification of the 'stability profile of mutant protein' (SPMP) data using mutant human lysozymes. , 1999, Protein engineering.

[209]  Tom Alber,et al.  Contributions of hydrogen bonds of Thr 157 to the thermodynamic stability of phage T4 lysozyme , 1988, Nature.

[210]  W. Lim,et al.  Thermal stabilities of mutant Escherichia coli tryptophan synthase α subunits , 1992 .

[211]  N. Xuan,et al.  A Comprehensive Alanine-Scanning Mutagenesis Study Reveals Roles for Salt Bridges in the Structure and Activity of Pseudomonas aeruginosa Elastase , 2015, PloS one.

[212]  M. Ishii,et al.  Stabilization of Pseudomonas aeruginosa Cytochromec 551 by Systematic Amino Acid Substitutions Based on the Structure of Thermophilic Hydrogenobacter thermophilus Cytochrome c 552 * , 1999, The Journal of Biological Chemistry.

[213]  P. Bryan,et al.  Large increases in general stability for subtilisin BPN' through incremental changes in the free energy of unfolding. , 1989, Biochemistry.

[214]  M. Oobatake,et al.  Conformational Stabilities of Escherichia coli RNase HI Variants with a Series of Amino Acid Substitutions at a Cavity within the Hydrophobic Core* , 1997, The Journal of Biological Chemistry.

[215]  B. Matthews,et al.  Structure and thermal stability of phage T4 lysozyme. , 1987, Methods in enzymology.

[216]  Georgios A. Dalkas,et al.  Cation–π, amino–π, π–π, and H‐bond interactions stabilize antigen–antibody interfaces , 2014, Proteins.

[217]  S. Tatulian,et al.  The sole tryptophan of amicyanin enhances its thermal stability but does not influence the electronic properties of the type 1 copper site. , 2014, Archives of biochemistry and biophysics.

[218]  R. Gray,et al.  Contribution of a single-turn alpha-helix to the conformational stability and activity of the alkaline proteinase inhibitor of Pseudomonas aeruginosa. , 2005, Biochemistry.

[219]  T. Herning,et al.  Role of proline residues in human lysozyme stability: a scanning calorimetric study combined with X-ray structure analysis of proline mutants. , 1994, Biochemistry.

[220]  D. Otzen,et al.  The Spectral and Thermodynamic Properties of Staphylococcal Enterotoxin A, E, and Variants Suggest That Structural Modifications Are Important to Control Their Function* , 2000, The Journal of Biological Chemistry.

[221]  J. Schellman,et al.  Stability of phage T4 lysozymes. I. Native properties and thermal stability of wild type and two mutant lysozymes. , 1977, Biochimica et biophysica acta.

[222]  W E Stites,et al.  Increasing the thermostability of staphylococcal nuclease: implications for the origin of protein thermostability. , 2000, Journal of molecular biology.

[223]  K. Yutani,et al.  Contribution of hydrogen bonds to the conformational stability of human lysozyme: calorimetry and X-ray analysis of six Ser --> Ala mutants. , 1999, Biochemistry.

[224]  L. A. Lipscomb,et al.  Context‐dependent protein stabilization by methionine‐to‐leucine substitution shown in T4 lysozyme , 1998, Protein science : a publication of the Protein Society.

[225]  C. Woodward,et al.  Crevice‐forming mutants of bovine pancreatic trypsin inhibitor: Stability changes and new hydrophobic surface , 1993, Protein science : a publication of the Protein Society.

[226]  C. D. Boone,et al.  Structural and catalytic effects of proline substitution and surface loop deletion in the extended active site of human carbonic anhydrase II , 2015, The FEBS journal.

[227]  Lisa D. Cabrita,et al.  In vitro and in silico design of alpha1-antitrypsin mutants with different conformational stabilities. , 2003, Journal of molecular biology.

[228]  J. G. Guillemette,et al.  Rational design of a more stable yeast iso-1-cytochrome c. , 1999, Biochimica et biophysica acta.

[229]  Michael Wunderlich,et al.  Stabilization of the cold shock protein CspB from Bacillus subtilis by evolutionary optimization of Coulombic interactions. , 2005, Journal of molecular biology.

[230]  F. Castellino,et al.  Role of tryptophan-74 of the recombinant kringle 2 domain of tissue-type plasminogen activator in its omega-amino acid binding properties. , 1992, Biochemistry.

[231]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[232]  B. Matthews,et al.  Hydrophobic packing in T4 lysozyme probed by cavity-filling mutants. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[233]  J. Otlewski,et al.  Amino‐acid substitutions at the fully exposed P1 site of bovine pancreatic trypsin inhibitor affect its stability , 2001, Protein science : a publication of the Protein Society.

[234]  B. Matthews,et al.  Alanine‐scanning mutagenesis of the β‐sheet region of phage T4 lysozyme suggests that tertiary context has a dominant effect on β‐sheet formation , 2004, Protein science : a publication of the Protein Society.

[235]  A. Fersht,et al.  Protein fragments as models for events in protein folding pathways: protein engineering analysis of the association of two complementary fragments of the barley chymotrypsin inhibitor 2 (CI-2). , 1995, Biochemistry.

[236]  M. Oobatake,et al.  Stabilization of Escherichia coli ribonuclease HI by strategic replacement of amino acid residues with those from the thermophilic counterpart. , 1992, The Journal of biological chemistry.

[237]  T. Poulos,et al.  Protein engineering of subtilisin BPN': enhanced stabilization through the introduction of two cysteines to form a disulfide bond. , 1987, Biochemistry.

[238]  G. D'alessio,et al.  Onconase: an unusually stable protein. , 2000, Biochemistry.

[239]  Volker Sieber,et al.  Surface‐exposed phenylalanines in the RNP1/RNP2 motif stabilize the cold‐shock protein CspB from Bacillus subtilis , 1998, Proteins.

[240]  G. Pielak,et al.  A native tertiary interaction stabilizes the A state of cytochrome c. , 1995, Biochemistry.

[241]  B. Matthews,et al.  Second-site revertants of an inactive T4 lysozyme mutant restore activity by restructuring the active site cleft. , 1991, Biochemistry.

[242]  B. Matthews,et al.  Design and structural analysis of alternative hydrophobic core packing arrangements in bacteriophage T4 lysozyme. , 1993, Journal of molecular biology.

[243]  M. Saito,et al.  Stabilization of hen egg white lysozyme by a cavity‐filling mutation , 2001, Protein science : a publication of the Protein Society.

[244]  D. Raleigh,et al.  Thermodynamics and kinetics of non-native interactions in protein folding: a single point mutant significantly stabilizes the N-terminal domain of L9 by modulating non-native interactions in the denatured state. , 2004, Journal of molecular biology.

[245]  S. Mazumdar,et al.  Thermodynamic effects of the alteration of the axial ligand on the unfolding of thermostable cytochrome C. , 2013, Biochemistry.

[246]  A. Sonawane,et al.  Improvement of stability and enzymatic activity by site-directed mutagenesis of E. coli asparaginase II. , 2014, Biochimica et biophysica acta.

[247]  Y. Yamagata,et al.  Contribution of polar groups in the interior of a protein to the conformational stability. , 2001, Biochemistry.

[248]  Yawen Bai,et al.  The folding pathway of barnase: the rate-limiting transition state and a hidden intermediate under native conditions. , 2004, Biochemistry.

[249]  W. J. Becktel,et al.  Protein stability curves , 1987, Biopolymers.

[250]  U. Hahn,et al.  X-ray crystallographic and calorimetric studies of the effects of the mutation Trp59-->Tyr in ribonuclease T1. , 1994, European journal of biochemistry.

[251]  T. Ueda,et al.  Relationship between local structure and stability in hen egg white lysozyme mutant with alanine substituted for glycine. , 2000, Protein engineering.

[252]  Bertrand Morel,et al.  A single mutation in an SH3 domain increases amyloid aggregation by accelerating nucleation, but not by destabilizing thermodynamically the native state , 2009, FEBS letters.

[253]  K. Siddiqui.  Some like it hot, some like it cold: Temperature dependent biotechnological applications and improvements in extremophilic enzymes. , 2015, Biotechnology advances.

[254]  A. Surolia,et al.  Thermodynamic effects of replacements of pro residues in helix interiors of maltose‐binding protein , 2003, Proteins.

[255]  J. Steyaert,et al.  Hydrophobic core manipulations in ribonuclease T1. , 2001, Biochemistry.

[256]  K. Takano,et al.  Role of amino acid residues at turns in the conformational stability and folding of human lysozyme. , 1999, Biochemistry.

[257]  Yuriko Yamagata,et al.  Buried water molecules contribute to the conformational stability of a protein. , 2003, Protein engineering.

[258]  H. J. Cha,et al.  Rescue of deleterious mutations by the compensatory Y30F mutation in ketosteroid isomerase , 2013, Molecules and cells.

[259]  F. Robb,et al.  Effects of a novel disulfide bond and engineered electrostatic interactions on the thermostability of azurin. , 2004, Biochemistry.

[260]  T. Haertlé,et al.  On the non‐respect of the thermodynamic cycle by DsbA variants , 2008, Protein science : a publication of the Protein Society.

[261]  Jian Tian,et al.  Thermal Stabilization of Dihydrofolate Reductase Using Monte Carlo Unfolding Simulations and Its Functional Consequences , 2015, PLoS Comput. Biol..

[262]  B. Matthews,et al.  Structural and thermodynamic analysis of the binding of solvent at internal sites in T4 lysozyme , 2001, Protein science : a publication of the Protein Society.

[263]  A. Fersht,et al.  An irregular beta-bulge common to a group of bacterial RNases is an important determinant of stability and function in barnase. , 1999, Journal of molecular biology.