Protein Structure and the Energetics of Protein Stability

Robertson, Andrew D.; Murphy, Kenneth P.

doi:10.1021/cr960383c

Cited by 627 publications

(710 citation statements)

References 101 publications

(294 reference statements)

Supporting

Mentioning

652

Contrasting

Unclassified

Order By: Relevance

“…This behavior is similar to that observed in the folding of proteins, 20,36,39 where the folding enthalpy is small at room temperature and becomes large and negative at high temperatures. Another similarity is that the difference in heat capacity between folded and unfolded states is independent of temperature.…”

Section: Resultssupporting

confidence: 85%

“…The nonvanishing positive value of ∆S was used to explain the scattered values of T s found in the analysis of a large set of proteins. 39 As mentioned before, one of the qualitative differences between small-and large-scale hydrophobicity in a strongly hydrophobic system is the occurrence of a drying transition. For interplate distances smaller than a critical value, D c , the confined water is thermodynamically unstable in its liquid phase and evaporates.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Temperature Dependence of Dimerization and Dewetting of Large-Scale Hydrophobes: A Molecular Dynamics Study

2008

View full text Add to dashboard Cite

We studied by molecular dynamics simulations the temperature dependence of hydrophobic association and drying transition of large-scale solutes. Similar to the behavior of small solutes, we found the association process to be characterized by a large negative heat capacity change. The origin of this large change in heat capacity is the high fragility of hydrogen bonds between water molecules at the interface with hydrophobic solutes; an increase in temperature breaks more hydrogen bonds at the interface than in the bulk. With increasing temperature, both entropy and enthalpy changes for association strongly decrease, while the change in free energy weakly varies, exhibiting a small minimum at high temperatures. At around T ) T s ) 360 K, the change in entropy is zero, a behavior similar to the solvation of small nonpolar solutes. Unexpectedly, we find that at T s , there is still a substantial orientational ordering of the interfacial water molecules relative to the bulk. Nevertheless, at this point, the change in entropy vanishes due to a compensating contribution of translational entropy. Thus, at T s , there is rotational order and translational disorder of the interfacial water relative to bulk water. In addition, we studied the temperature dependence of the drying-wetting transition. By calculating the contact angle of water on the hydrophobic surface at different temperatures, we compared the critical distance observed in the simulations with the critical distance predicted by macroscopic theory. Although the deviations of the predicted from the observed values are very small (8-23%), there seems to be an increase in the deviations with an increase in temperature. We suggest that these deviations emerge due to increased fluctuations, characterizing finite systems, as the temperature increases.

show abstract

Section: Resultssupporting

confidence: 85%

Section: Introductionmentioning

confidence: 92%

Temperature Dependence of Dimerization and Dewetting of Large-Scale Hydrophobes: A Molecular Dynamics Study

2008

View full text Add to dashboard Cite

show abstract

“…1. In recent decades many of the studies carried out on proteins have used DSC to examine the reversible folding/unfolding transition of globular proteins under equilibrium conditions, focusing on the elucidation of the thermodynamic properties of protein folding and stability (Makhatadze and Privalov 1995;Robertson and Murphy 1997;Privalov and Dragan 2007). In contrast, relatively few attempts have been made to use DSC to characterize the thermodynamics of amyloid fibril formation and stability, possibly due to the irreversibility of protein aggregation, the complex nature of the aggregates, and the lack of a theoretical model to interpret the DSC data.…”

Section: Introductionmentioning

confidence: 99%

Application and use of differential scanning calorimetry in studies of thermal fluctuation associated with amyloid fibril formation

Sasahara

Goto

2012

Biophys Rev

View full text Add to dashboard Cite

The aggregation of proteins into amyloid fibrils is a topic that has attracted great interest because the process is associated with the pathology of numerous human diseases. Despite considerable progress in the elucidation of the structure of amyloid fibrils and the kinetic mechanism of their formation, knowledge on the thermodynamic aspects underlying the formation and stability of amyloid fibrils is limited. In this review, we summarize recent calorimetric studies of amyloid fibril formation, with the goal of obtaining a better understanding of the causal factors that thermally induce proteins to aggregate into amyloid fibrils. Calorimetric data show that differential scanning calorimetry is a useful technique to study the causative factors that thermally trigger the conversion to the amyloid structure and highlight the physics related to the thermal fluctuation of proteins during this conversion.

show abstract

“…Myers et al established the strong correlation between m values, the dependence of the free energy of unfolding on denaturant concentration, and the change in a surface area of protein exposed to solvent upon unfolding (ΔASA), and between ΔASA and ΔC p , change of molar heat capacity at constant pressure, for a large set of proteins [15]. Robertson et al reported similar results with 49 different proteins [16], indicating that ΔC p is proportional to the number of residues further supporting ΔASA to ΔC p correlation.…”

Section: Introductionmentioning

confidence: 92%

Thermodynamic characterization for the denatured state of bovine prion protein and the BSE Associated variant E211K

Hwang

Nicholson

2018

Prion

View full text Add to dashboard Cite

Propagation of transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrPC, into a misfolded oligomeric form, PrPSc. The most common hereditary prion disease is a genetic form of Creutzfeldt-Jakob disease in humans, in which a mutation in the prion gene results in a glutamic acid to lysine substitution at position 200 (E200K) in PrP. In cattle, the analogous amino acid substitution is found at residue 211 (E211K) and has been associated with a case of bovine spongiform encephalopathy. Here, we have compared the secondary structure of E211K to that of wild type using circular dichroism and completed a thermodynamic analysis of the folding of recombinant wild type and E211K variants of the bovine prion protein. The secondary structure of the E211K variant was essentially indistinguishable from that of wild type. The thermodynamic stability of E211K substitution showed a slight destabilization relative to the wild type consistent with results reported for recombinant human prion protein and its mutant E200K. In addition, the E211K variant exhibits a similarly compact denatured state to that of wild type based upon similar m-value and change in heat capacity of unfolding for the proteins. Together these results indicate that residual structure in the denatured state of bPrP is present in both the wild type protein and BSE associated variant E211K. Given this observation, as well as folding similarities reported for other disease associated variants of PrP it is worth consideration that functional aspects of PrP conformation may play a role in the misfolding process.

show abstract

Protein Structure and the Energetics of Protein Stability

Cited by 627 publications

References 101 publications

Temperature Dependence of Dimerization and Dewetting of Large-Scale Hydrophobes: A Molecular Dynamics Study

Temperature Dependence of Dimerization and Dewetting of Large-Scale Hydrophobes: A Molecular Dynamics Study

Application and use of differential scanning calorimetry in studies of thermal fluctuation associated with amyloid fibril formation

Thermodynamic characterization for the denatured state of bovine prion protein and the BSE Associated variant E211K

Contact Info

Product

Resources

About