Mutational studies of protein structures and their stabilities

Graph theory

1969 • 11,244 citations

On the nature of allosteric transitions: A plausible model

1965 • 8,699 citations

Some Factors in the Interpretation of Protein Denaturation

1959 • 4,817 citations

Dominant forces in protein folding

1990 • 3,682 citations

Comparison of Experimental Binding Data and Theoretical Models in Proteins Containing Subunits^*

1966 • 2,956 citations

Enzyme structure and mechanism

1977 • 2,935 citations

Enzyme structure and mechanism

1978 • 2,897 citations

AREAS, VOLUMES, PACKING, AND PROTEIN STRUCTURE

1977 • 2,631 citations

Stability of Proteins Small Globular Proteins

1979 • 2,139 citations

Protein Denaturation

1968 • 2,108 citations

Hydrogen bonding in globular proteins

1984 • 1,760 citations

Unfolding free energy changes determined by the linear extrapolation method. 1. Unfolding of phenylmethanesulfonyl .alpha.-chymotrypsin using different denaturants

1988 • 1,568 citations

Protein denaturation. C. Theoretical models for the mechanism of denaturation.

1970 • 1,550 citations

Tertiary templates for proteins

1987 • 1,485 citations

High-Resolution Epitope Mapping of hGH-Receptor Interactions by Alanine-Scanning Mutagenesis

1989 • 1,357 citations

Dynamics of Proteins and Nucleic Acids

1988 • 1,274 citations

Protein Denaturation

1970 • 1,264 citations

Dynamics of Proteins and Nucleic Acids

1987 • 1,222 citations

Enthalpy–entropy compensation phenomena in water solutions of proteins and small molecules: A ubiquitous properly of water

1970 • 1,173 citations

Protein stability curves

1987 • 990 citations

A General Method for Site-specific Incorporation of Unnatural Amino Acids into Proteins

1989 • 989 citations

Response of a Protein Structure to Cavity-Creating Mutations and Its Relation to the Hydrophobic Effect

1992 • 933 citations

Structural characterization of folding intermediates in cytochrome c by H-exchange labelling and proton NMR

1988 • 823 citations

Protein Hydration in Aqueous Solution

1991 • 778 citations

Enhanced protein thermostability from site-directed mutations that decrease the entropy of unfolding.

1987 • 738 citations

Additivity of mutational effects in proteins

1990 • 652 citations

Mechanisms of cooperativity and allosteric regulation in proteins

1989 • 615 citations

NMR evidence for an early framework intermediate on the folding pathway of ribonuclease A

1988 • 583 citations

The use of double mutants to detect structural changes in the active site of the tyrosyl-tRNA synthetase (Bacillus stearothermophilus)

1984 • 563 citations

Mechanisms of cooperativity and allosteric regulation in proteins

1990 • 514 citations

pH-Induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme

1990 • 503 citations

Characterization of a partly folded protein by NMR methods: studies on the molten globule state of guinea pig .alpha.-lactalbumin

1989 • 473 citations

Conformational stability and activity of ribonuclease T1 with zero, one, and two intact disulfide bonds.

1988 • 445 citations

Crystallographic studies of the dynamic properties of lysozyme

1979 • 437 citations

Strength and co-operativity of contributions of surface salt bridges to protein stability

1990 • 415 citations

Contribution of hydrophobic interactions to protein stability

1988 • 413 citations

Conformational stability of globular proteins

1990 • 390 citations

Alternative packing arrangements in the hydrophobic core of λrepresser

1989 • 375 citations

Hydrophobic stabilization in T4 lysozyme determined directly by multiple substitutions of Ile 3

1988 • 375 citations

Contributions of the large hydrophobic amino acids to the stability of staphylococcal nuclease

1990 • 372 citations

Capping and α-helix stability

1989 • 363 citations

Protein structure determination in solution by NMR spectroscopy.

1990 • 352 citations

Energetics of complementary side chain packing in a protein hydrophobic core

1989 • 346 citations

THE THERMODYNAMIC STABILITY OF PROTEINS

1987 • 338 citations

Combinatorial Cassette Mutagenesis as a Probe of the Informational Content of Protein Sequences

1988 • 326 citations

Molecular Code for Cooperativity in Hemoglobin

1992 • 322 citations

Aromatic-aromatic interactions and protein stability

1991 • 321 citations

Determinants of visual pigment absorbance: identification of the retinylidene Schiff's base counterion in bovine rhodopsin

1990 • 319 citations

MUTATIONAL EFFECTS ON PROTEIN STABILITY

1989 • 311 citations

Disulfide Bond Engineered into T4 Lysozyme: Stabilization of the Protein Toward Thermal Inactivation

1984 • 311 citations

Tinkering with Enzymes: What Are We Learning?

1987 • 304 citations

Mutant forms of staphylococcal nuclease with altered patterns of guanidine hydrochloride and urea denaturation

1986 • 275 citations

Structural and thermodynamic consequences of burying a charged residue within the hydrophobic core of T4 lysozyme

1991 • 265 citations

Structural basis of the allosteric behaviour of phosphofructokinase

1990 • 262 citations

Fluctuations in Protein Structure from X-Ray Diffraction

1984 • 254 citations

Temperature-sensitive mutations of bacteriophage T4 lysozyme occur at sites with low mobility and low solvent accessibility in the folded protein

1987 • 253 citations

A peptide model of a protein folding intermediate

1988 • 252 citations

Fourier Transform Infrared Techniques for Probing Membrane Protein Structure

1988 • 248 citations

Dependence of conformational stability on hydrophobicity of the amino acid residue in a series of variant proteins substituted at a unique position of tryptophan synthase alpha subunit.

1987 • 247 citations

Residual structure in large fragments of staphylococcal nuclease: effects of amino acid substitutions

1989 • 234 citations

Functional Role of Aspartic Acid-27 in Dihydrofolate Reductase Revealed by Mutagenesis

1986 • 233 citations

A mutant T4 lysozyme displays five different crystal conformations

1990 • 231 citations

Stabilization of protein structure by interaction of α-helix dipole with a charged side chain

1988 • 229 citations

Genetic and structural analysis of the protein stability problem

1987 • 227 citations

Protein engineering of subtilisin BPN': enhanced stabilization through the introduction of two cysteines to form a disulfide bond

1987 • 224 citations

EFFECTS OF SITE-SPECIFIC AMINO ACID MODIFICATION ON PROTEIN INTERACTIONS AND BIOLOGICAL FUNCTION

1985 • 224 citations

Free energy perturbation calculations on binding and catalysis after mutating Asn 155 in subtilisin

1987 • 221 citations

GENETIC ANALYSIS OF PROTEIN STABILITY AND FUNCTION

1989 • 214 citations

The role of internal packing interactions in determining the structure and stability of a protein

1991 • 208 citations

Unfolding free energy changes determined by the linear extrapolation method. 2. Incorporation of .DELTA.G.degree.N-U values in a thermodynamic cycle

1988 • 203 citations

Site-Specific Incorporation of Novel Backbone Structures into Proteins

1992 • 189 citations

The crystallographically determined structures of atypical strained disulfides engineered into subtilisin.

1986 • 182 citations

Accurate prediction of the stability and activity effects of site-directed mutagenesis on a protein core

1991 • 180 citations

Probing the stability of a partly folded apomyoglobin intermediate by site-directed mutagenesis

1991 • 179 citations

Influence of Interior Packing and Hydrophobicity on the Stability of a Protein

1989 • 173 citations

Relationships between apparent binding energies measured in site-directed mutagenesis experiments and energetics of binding and catalysis

1988 • 172 citations

Proline isomerism in staphylococcal nuclease characterized by NMR and site-directed mutagenesis

1987 • 167 citations

Disulfide bonds and thermal stability in T4 lysozyme.

1988 • 165 citations

Analysis of the interaction between charged side chains and the .alpha.-helix dipole using designed thermostable mutants of phage T4 lysozyme

1991 • 164 citations

Structural and energetic consequences of disruptive mutations in a protein core

1992 • 164 citations

In a staphylococcal nuclease mutant the side-chain of a lysine replacing valine 66 is fully buried in the hydrophobic core

1991 • 162 citations

Simulation analysis of the stability mutant R96H of T4 lysozyme

1991 • 162 citations

Distal residues in the oxygen binding site of haemoglobin studied by protein engineering

1987 • 160 citations

Reverse hydrophobic effects relieved by amino-acid substitutions at a protein surface

1990 • 157 citations

Yeast cytochrome c peroxidase: mutagenesis and expression in Escherichia coli show tryptophan-51 is not the radical site in compound I

1987 • 157 citations

[3] Measurements of preferential solvent interactions by densimetric techniques

1979 • 154 citations

Effect of single amino acid replacements on the thermal stability of the NH2-terminal domain of phage lambda repressor.

1984 • 153 citations

An engineered intersubunit disulfide enhances the stability and DNA binding of the N-terminal domain of .lambda. repressor

1986 • 149 citations

Thermodynamic stability and point mutations of bacteriophage T4 lysozyme

1984 • 149 citations

Stability mutants of staphylococcal nuclease: large compensating enthalpy-entropy changes for the reversible denaturation reaction

1988 • 149 citations

Quantitative interpretations of double mutations of enzymes

1992 • 145 citations

Escherichia coli aspartate transcarbamoylase: the molecular basis for a concerted allosteric transition

1990 • 143 citations

Contribution of the hydrophobic effect to protein stability: analysis based on simulations of the Ile-96----Ala mutation in barnase.

1991 • 136 citations

Probing the Determinants of Protein Folding and Stability with Amino Acid Substitutions

1989 • 133 citations

An engineered disulfide bond in dihydrofolate reductase

1987 • 133 citations

Replacements of Pro ⁸⁶ in Phage T4 Lysozyme Extend an α-Helix But Do Not Alter Protein Stability

1988 • 131 citations

Design and structural analysis of alternative hydrophobic core packing arrangements in bacteriophage T4 lysozyme

1992 • 130 citations

Modeling the effects of mutations on the denatured states of proteins

1992 • 126 citations

Triosephosphate isomerase: removal of a putatively electrophilic histidine residue results in a subtle change in catalytic mechanism

1988 • 126 citations

Use of site-directed mutagenesis to destabilize native apomyoglobin relative to folding intermediates

1989 • 124 citations

Kinetic and magnetic resonance studies of effects of genetic substitution of a calcium-liganding amino acid in staphylococcal nuclease

1986 • 122 citations

Contributions of the polar, uncharged amino acids to the stability of staphylococcal nuclease: evidence for mutational effects on the free energy of the denatured state

1992 • 122 citations

X-ray structures of recombinant yeast cytochrome c peroxidase and three heme-cleft mutants prepared by site-directed mutagenesis

1990 • 119 citations

Site-directed mutagenesis shows that tyrosine 248 of carboxypeptidase A does not play a crucial role in catalysis

1985 • 117 citations

Stabilization of λ repressor against thermal denaturation by site‐directed Gly→Ala changes in α‐helix 3

1986 • 115 citations

Urea dependence of thiol-disulfide equilibria in thioredoxin: confirmation of the linkage relationship and a sensitive assay for structure

1989 • 115 citations

Rigid protein motion as a model for crystallographic temperature factors.

1991 • 114 citations

Construction of a functional lactose permease devoid of cysteine residues

1991 • 111 citations

Energetics of repacking a protein interior.

1991 • 111 citations

The Formation of Anhydrochymotrypsin by Removing the Elements of Water from the Serine at the Active Site¹

1966 • 109 citations

Free energy calculations on protein stability: Thr-157 .fwdarw. Val-157 mutation of T4 lysozyme

1989 • 108 citations

Multiple conformations of a protein demonstrated by magnetization transfer NMR spectroscopy

1986 • 103 citations

Genetic Studies of Protein Stability and Mechanisms of Folding

1988 • 102 citations

Changes in crystallographic structure and thermostability of a Cu,Zn superoxide dismutase mutant resulting from the removal of a buried cysteine.

1990 • 101 citations

The protein-folding problem: the native fold determines packing, but does packing determine the native fold?

1991 • 101 citations

Protein stability and electrostatic interactions between solvent exposed charged side chains

1990 • 97 citations

Protein structure, folding and design

1985 • 93 citations

Site-directed mutants of staphylococcal nuclease. Detection and localization by proton NMR spectroscopy of conformational changes accompanying substitutions for glutamic acid-43

1987 • 92 citations

Structural effects induced by removal of a disulfide-bridge: the X-ray structure of the C30A/C51A mutant of basic pancreatic trypsin inhibitor at 1.6 Å

1990 • 92 citations

The mechanism of protein folding

1991 • 91 citations

Changes in crystallographic structure and thermostability of a Cu,Zn superoxide dismutase mutant resulting from the removal of a buried cysteine.

1990 • 89 citations

Thermostability of Temperature-sensitive Folding Mutants of the P22 Tailspike Protein

1989 • 88 citations

Cumulative site-directed charge-change replacements in bacteriophage T4 lysozyme suggest that long-range electrostatic interactions contribute little to protein stability

1991 • 86 citations

Accommodation of single amino acid insertions by the native state of staphylococcal nuclease

1990 • 80 citations

Toward a simplification of the protein folding problem: a stabilizing polyalanine .alpha.-helix engineered in T4 lysozyme

1991 • 79 citations

Structural and thermodynamic analysis of the packing of two α-helices in bacteriophage T4 lysozyme

1991 • 78 citations

A scanning calorimetric study of the thermal denaturation of the lysozyme of phage T4 and the Arg 96 .fwdarw. His mutant form thereof

1989 • 77 citations

Conformational stability and activity of ribonuclease T1 and mutants

1989 • 75 citations

Identification of electrostatic interactions that determine the phosphorylation site specificity of the cAMP-dependent protein kinase

1991 • 75 citations

Effects of multiple replacements at a single position on the folding and stability of dihydrofolate reductase from Escherichia coli

1989 • 70 citations

Variability of conformations at crystal contacts in BPTI represent true low‐energy structures: Correspondence among lattice packing and molecular dynamics structures

1992 • 69 citations

Effect of single amino acid replacements on the folding and stability of dihydrofolate reductase from Escherichia coli

1987 • 67 citations

Structural Studies of Mutants of T4 Lysozyme That Alter Hydrophobic Stabilization

1989 • 67 citations

A differential scanning calorimetric study of the thermal unfolding of seven mutant forms of phage T4 lysozyme

1991 • 66 citations

Structural studies of mutants of the lysozyme of bacteriophage T4

1987 • 65 citations

THE HEMOGLOBIN TETRAMER: A Three-State Molecular Switch for Control of Ligand Affinity

1987 • 64 citations

Escherichia coli aspartate carbamoyltransferase: the probing of crystal structure analysis via site-specific mutagenesis

1991 • 63 citations

Long-range electrostatic interactions can influence the folding, stability, and cooperativity of dihydrofolate reductase

1989 • 63 citations

Structure of proteins with single-site mutations: a minimum perturbation approach.

1985 • 61 citations

Dihydrofolate reductase: multiple conformations and alternative modes of substrate binding

1989 • 61 citations

THE CHEMICAL MODIFICATION OF ENZYMATIC SPECIFICITY

1985 • 57 citations

Tolerance of T4 lysozyme to proline substitutions within the long interdomain alpha-helix illustrates the adaptability of proteins to potentially destabilizing lesions.

1992 • 53 citations

Protein Structure, Folding and Design

1988 • 53 citations

Approach to the tertiary structure of globular proteins

1975 • 50 citations

Effects of denaturants at low concentrations on the reversible denaturation of staphylococcal nuclease

1989 • 49 citations

Mutational analysis of protein stability

1991 • 49 citations

Conversion of allosteric inhibition to activation in phosphofructokinase by protein engineering

1987 • 48 citations

Engineering enzyme subsite specificity: preparation, kinetic characterization, and x-ray analysis at 2.0-.ANG. resolution of Val111Phe site-mutated calf chymosin

1990 • 48 citations

Hydrogen-1 NMR evidence for three interconverting forms of staphylococcal nuclease: effects of mutations and solution conditions on their distribution

1989 • 48 citations

Heterotropic effectors promote a global conformational change in aspartate transcarbamoylase

1990 • 45 citations

Structure of a stabilizing disulfide bridge mutant that closes the active‐site cleft of T4 lysozyme

1992 • 43 citations

Hydrophobic interactions via mutants of Escherichia coli dihydrofolate reductase: separation of binding and catalysis

1989 • 42 citations

Nuclear Magnetic Resonance Studies of the Structure and Binding Sites of Enzymes, XII. A Conformational Equilibrium in Staphylococcal Nuclease Involving a Histidine Residue

1970 • 42 citations

Identification of the intermediate allosteric species in human hemoglobin reveals a molecular code for cooperative switching.

1991 • 40 citations

Crystal structures of two engineered thiol trypsins

1989 • 39 citations

High-resolution structure of the temperature-sensitive mutant of phage lysozyme, Arg 96 .fwdarw. His

1989 • 39 citations

Active site mutant Glu-43 .fwdarw. Asp in staphylococcal nuclease displays nonlocal structural changes

1990 • 38 citations

Insertion of new sequences into the catalytic domain of an enzyme

1989 • 38 citations

Synergism in folding of a double mutant of the .alpha. subunit of tryptophan synthase

1986 • 38 citations

Investigation of transition-state stabilization by residues histidine-45 and threonine-40 in the tyrosyl-tRNA synthetase

1987 • 38 citations

Structural and energetic differences between insertions and substitutions in staphylococcal nuclease

1992 • 35 citations

Investigation of the functional role of tryptophan-22 in Escherichia coli dihydrofolate reductase by site-directed mutagenesis

1991 • 34 citations

Crystal structure of subtilisin BPN′ variants containing disulfide bonds and cavities: Concerted structural rearrangements induced by mutagenesis

1990 • 34 citations

The regulatory subunit of Escherichia coli aspartate carbamoyltransferase may influence homotropic cooperativity and heterotropic interactions by a direct interaction with the loop containing residues 230-245 of the catalytic chain.

1990 • 30 citations

Crystal structure of the ASP-199.fwdarw.asparagine mutant of chloramphenicol acetyltransferase to 2.35.ANG. resolution: structural consequences of disruption of a buried salt bridge

1990 • 30 citations

Effects of point mutations in a hinge region on the stability, folding, and enzymic activity of Escherichia coli dihydrofolate reductase

1991 • 29 citations

Hazards and their exploitation in the applications of molecular biology to structure-function relationships

1990 • 28 citations

Structural analysis of the temperature-sensitive mutant of bacteriophage T4 lysozyme, glycine 156----aspartic acid.

1987 • 28 citations

Role of tyrosine-80 in the stability of kanamycin nucleotidyltransferase analyzed by site-directed mutagenesis

1988 • 27 citations

Constraints on amino acid substitutions in the N-terminal helix of cytochrome c explored by random mutagenesis

1991 • 26 citations

Structural analysis of the temperature-sensitive mutant of bacteriophage T4 lysozyme, glycine 156→aspartic acid.

1987 • 26 citations

Designing an allosterically locked phosphofructokinase

1991 • 24 citations

Hemoglobins

1991 • 24 citations

Crystallographic phasing and refinement of macromolecules

1991 • 23 citations

New molecular biology methods for protein engineering

1991 • 22 citations

Repacking protein interiors

1991 • 21 citations

Mutant aminoacyl-tRNA synthetase that compensates for a mutation in the major identity determinant of its tRNA

1991 • 19 citations

CONFORMATIONAL STABILITY OF GLOBULAR PROTEINS

1990 • 19 citations

Crystal structure of rat trypsin-S195C at −150 °C

1991 • 17 citations

Ubiquitin Function Studied by Disulfide Engineering

1989 • 15 citations

Structural aspects of allostery

1991 • 15 citations

Co-operative interactions between the catalytic sites in Escherichia coli aspartate transcarbamylase

1990 • 14 citations

Crystallographic analysis of trypsin-G226A

1991 • 13 citations

Experimental NMR techniques for studies of biopolymers

1991 • 13 citations

Mapping catalytically important regions of an enzyme using two-codon insertion mutagenesis: a case study correlating β-lactamase mutants with the three-dimensional structure

1991 • 12 citations

4 Analysis of Protein Function by Mutagenesis

1990 • 11 citations

Resolution of a protein sequence ambiguity by X-ray crystallographic and mass spectrometric methods

1992 • 8 citations

Specific suppression of heterotropic interactions in phosphofructokinase by the mutation of leucine 178 into tryptophan.

1990 • 8 citations

Molecular mechanical potential functions and their application to study molecular systems

1991 • 8 citations

New molecular biology methods for protein engineering

1991 • 4 citations

Effects of Mutations on Thermodynamic Properties of Proteins

1993 • 2 citations