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At least 343 records · Page 19Linked to original sources
PubMed2007

Hydrophobic interaction chromatography of proteins. II. Solution thermodynamic properties as a determinant of retention.

A general thermodynamic relation was derived to correlate protein solubility to retention in hydrophobic interaction chromatography (HIC). This relation is built on a thermodynamic formulation presented previously by Melander, Horváth and co-workers in the context of the solvophobic theory, but the final result is independent of this model framework. The relation reflects an increase in protein retention in HIC under conditions that promote precipitation or crystallization, consistent with early descriptions of HIC. To examine the contribution of protein solubility to retention in HIC, isocratic elution experiments were performed with four different commercially available agarose media and four model proteins (ribonuclease A (RNA), lysozyme (LYS), myoglobin (MYO), and ovalbumin (OVA)). A wide variety of retention trends were observed as a function of protein, adsorbent type, salt type and concentration, and pH. In general, however, the results show that solubility, or its surrogate, the second osmotic virial coefficient, which reflects solution thermodynamic properties, correlates well with HIC retention in many cases; this includes correctly predicting reverse Hofmeister effects, which cannot be explained by retention models based on the solvophobic theory and preferential interaction theory. However, solution properties could not explain retention behavior under some conditions. In those cases, effects such as protein-surface interactions or conformational change could be important determinants of protein adsorption.

Chromatography, High Pressure Liquid↗
PubMed2006

Thermodynamics and stability of the PAAD/DAPIN/PYRIN domain of IFI-16.

The PAAD domain is a conserved domain recently identified in more than 35 human proteins that are involved in apoptosis and inflammatory signaling pathways. Structural studies have confirmed that this domain belongs to the death domain superfamily which includes PAAD/CARD/DED/DD families. Recently, the 3D structures determined by NMR of NALP1 and ASC PAAD domain, members of the PAAD family, have shown that it is composed of a 6 helix bundle as with other death domain family members. However, helix-3 in the solved structures is unordered in solution. In this study we compare the thermodynamic, folding and stability properties of different members of the PAAD and CARD families and investigate structural conformational changes induced by the helix inducers trifluoroethanol and SDS on the PAAD domain of IFI16 and on the CARD domain of RAIDD. We show that inside the PAAD and CARD families, members have similar thermodynamic properties, however, the DeltaG of folding for PAAD and CARD members are, respectively, -1.4 and -5.5 kcal mol(-1). This difference is attributed to less alpha helical content for PAAD due to the unfolding of helix-3 that lowers bonded energy and increases disorder when compared to CARD members. Despite identical fold between PAAD and CARD families but limited sequence identity, there are striking differences in the thermodynamics of both families.

Amino Acid Sequence↗
PubMed2006

Analysis of ligand binding curves on basis of mean intrinsic thermodynamic quantities.

The mean intrinsic thermodynamic quantity can be defined by considering the relative population of complex species in the solution and the value of intrinsic thermodynamic quantity corresponds to each step of ligation. In the present study a new method is introduced for analysis of experimental ligand binding data on basis of mean intrinsic thermodynamic quantities. In this regard, a deviation parameter was defined by comparing the non-interacting system with the cooperative interactive one. This parameter can be calculated just by estimation of the first binding constant. A set of relations between this deviation parameter and other binding characteristics, such as mean intrinsic Gibbs free energy of binding and mean Gibbs free energy of site-site interaction, have been developed. This model presents binding mechanism in a unified way that is simple, yet stringent, more straightforward, more reliable and informative. This analyzing method has been successfully applied for evaluation of various systems such as oxygen binding to hemoglobin, laurate and warfarin binding to human serum albumin, and reveals some new biological features of these binding systems.

Hemoglobins↗
PubMed2005

Thermodynamics of microbial growth and metabolism: an analysis of the current situation.

This paper attempts to review in how far thermodynamic analysis can be used to understand and predict the performance of microorganisms with respect to growth and bio-product synthesis. In the first part, a simple thermodynamic model of microbial growth is developed which explains the relationship between the driving force for growth in terms of Gibbs energy dissipation and biomass yield. From the currently available literature, it appears that the Gibbs energy dissipation per C-mol of biomass grown, which represents the driving force for chemotrophic growth, may have been adapted by evolutionary processes to strike a reasonable compromise between metabolic rate and growth efficiency. Based on empirical correlations of the C-molar Gibbs energy dissipation, the wide variety of biomass yields observed in nature can be explained and roughly predicted. This type of analysis may be highly useful in environmental applications, where such wide variations occur. It is however not able to predict biomass yields in very complex systems such as mammalian cells nor is it able to predict or to assess bio-product or recombinant protein yields. For this purpose, a much more sophisticated treatment that accounts for individual metabolic pathways separately is required. Based on glycolysis as a test example, it is shown in the last part that simple thermodynamic analysis leads to erroneous conclusions even in well-known, simple cases. Potential sources for errors have been analyzed and can be used to identify the most important needs for future research.

Bacteria↗
PubMed2004

A thermodynamic basis of DNA sequence selectivity by the ETS domain of murine PU.1.

The ETS domain of the transcription factor PU.1 tolerates a large number of DNA cognate variants that differ exclusively in the sequences flanking a critical central consensus, 5'-GGAA-3'. We investigated the thermodynamics of site selection by the DNA-binding domain by following the PU.1 ETS/DNA equilibrium with a large set of cognate variants under various temperature and salt conditions by filter binding. Our results indicate that the stability of the ETS/DNA complex is quantitatively tied to variations in the change in heat capacity. Thermodynamic effects induced by changing Na(+) concentrations from 150 mM to 250 mM are complex and not readily interpreted by polyelectrolyte theory. We also extended our understanding of data from our previous investigation on energetic base-neighbour coupling, by dissecting the thermodynamic contributions underlying the observed free-energy coupling. In conjunction with available structural and biochemical data, we propose that site selectivity by the PU.1 ETS domain arises from differential protein/DNA contacts in the flanking sequences that modulate the orientation of the ETS recognition helix and trigger a coupled reduction in the flexibility observed in the unbound ETS domain.

Animals↗
PubMed2004

Genomic determinants of protein folding thermodynamics in prokaryotic organisms.

Here we investigate how thermodynamic properties of orthologous proteins are influenced by the genomic environment in which they evolve. We performed a comparative computational study of 21 protein families in 73 prokaryotic species and obtained the following main results. (i) Protein stability with respect to the unfolded state and with respect to misfolding are anticorrelated. There appears to be a trade-off between these two properties, which cannot be optimized simultaneously. (ii) Folding thermodynamic parameters are strongly correlated with two genomic features, genome size and G+C composition. In particular, the normalized energy gap, an indicator of folding efficiency in statistical mechanical models of protein folding, is smaller in proteins of organisms with a small genome size and a compositional bias towards A+T. Such genomic features are characteristic for bacteria with an intracellular lifestyle. We interpret these correlations in light of mutation pressure and natural selection. A mutational bias toward A+T at the DNA level translates into a mutational bias toward more hydrophobic (and in general more interactive) proteins, a consequence of the structure of the genetic code. Increased hydrophobicity renders proteins more stable against unfolding but less stable against misfolding. Proteins with high hydrophobicity and low stability against misfolding occur in organisms with reduced genomes, like obligate intracellular bacteria. We argue that they are fixed because these organisms experience weaker purifying selection due to their small effective population sizes. This interpretation is supported by the observation of a high expression level of chaperones in these bacteria. Our results indicate that the mutational spectrum of a genome and the strength of selection significantly influence protein folding thermodynamics.

Archaea↗
PubMed2005

Two different T cell receptors use different thermodynamic strategies to recognize the same peptide/MHC ligand.

A6 and B7 are two alphabeta T cell receptors (TCRs) that recognize the Tax peptide presented by the class I major histocompatibility molecule HLA-A2 (Tax/HLA-A2). Despite the fact that the two TCRs have different CDR loops and use different amino acid residues to contact their ligand, both receptors bind ligand with similar diagonal orientations. Here we show that they also bind with very similar binding affinities and kinetics (the DeltaDeltaG degrees for binding is approximately 0.3kcal/mol at 25 degrees C). The two receptors respond similarly to alterations in the MHC molecule, yet differ dramatically in their responses to ionic strength and temperature. The different responses to temperature indicate markedly different binding thermodynamics, which are not predictable from the surface area buried in the interfaces. A6 and B7 thus represent two TCRs that are both compatible with Tax/HLA-A2, although compatibility has been achieved through the use of different thermodynamic strategies. Finally, neither A6 nor B7 are predicted to undergo large conformational adaptations upon binding, distinguishing them from a number of other TCRs whose structure, thermodynamics, and kinetics have been characterized.

Gene Products, tax↗
PubMed2005

Thermodynamic and structural equivalence of two HLA-B27 subtypes complexed with a self-peptide.

The F pocket of major histocompatibility complex (in humans HLA) class I molecules accommodates the C terminus of the bound peptide. Residues forming this pocket exhibit considerable polymorphism, and a single difference (Asp116 in HLA-B*2705 and His116 in HLA-B*2709 heavy chains) confers differential association of these two HLA-B27 subtypes to the autoimmune disease ankylosing spondylitis. As peptide presentation by HLA molecules is of central importance for immune responses, we performed thermodynamic (circular dichroism, differential scanning calorimetry, fluorescence polarization) and X-ray crystallographic analyses of both HLA-B27 subtypes complexed with the epidermal growth factor response factor 1-derived self-peptide TIS (RRLPIFSRL) to understand the impact of the Asp116His exchange on peptide display. This peptide is known to be presented in vivo by both subtypes, and as expected for a self-peptide, TIS-reactive cytotoxic T lymphocytes are absent in the respective individuals. The thermodynamic analyses reveal that both HLA-B27:TIS complexes exhibit comparable, relatively high thermostability (Tm approximately 60 degrees C) and undergo multi-step unfolding reactions, with dissociation of the peptide in the first step. As shown by X-ray crystallography, only subtle structural differences between the subtypes were observed regarding the architecture of their F pockets, including the presence of distinct networks of water molecules. However, no consistent structural differences were found between the peptide presentation modes. In contrast to other peptides displayed by the two HLA-subtypes which show either structural or dynamical differences in their peptide presentation modes, the TIS-complexed HLA-B*2705 and HLA-B*2709 subtypes are an example for thermodynamic and structural equivalence, in agreement with functional data.

Binding Sites↗
PubMed2006

Thermodynamic penalty arising from burial of a ligand polar group within a hydrophobic pocket of a protein receptor.

Here, we examine the thermodynamic penalty arising from burial of a polar group in a hydrophobic pocket that forms part of the binding-site of the major urinary protein (MUP-I). X-ray crystal structures of the complexes of octanol, nonanol and 1,8 octan-diol indicate that these ligands bind with similar orientations in the binding pocket. Each complex is characterised by a bridging water molecule between the hydroxyl group of Tyr120 and the hydroxyl group of each ligand. The additional hydroxyl group of 1,8 octan-diol is thereby forced to reside in a hydrophobic pocket, and isothermal titration calorimetry experiments indicate that this is accompanied by a standard free energy penalty of +21 kJ/mol with respect to octanol and +18 kJ/mol with respect to nonanol. Consideration of the solvation thermodynamics of each ligand enables the "intrinsic" (solute-solute) interaction energy to be determined, which indicates a favourable enthalpic component and an entropic component that is small or zero. These data indicate that the thermodynamic penalty to binding derived from the unfavourable desolvation of 1,8 octan-diol is partially offset by a favourable intrinsic contribution. Quantum chemical calculations suggest that this latter contribution derives from favourable solute-solute dispersion interactions.

Binding Sites↗
PubMed2004

Thermodynamic constraints for biochemical networks.

The constraint-based approach to analysis of biochemical systems has emerged as a useful tool for rational metabolic engineering. Flux balance analysis (FBA) is based on the constraint of mass conservation; energy balance analysis (EBA) is based on non-equilibrium thermodynamics. The power of these approaches lies in the fact that the constraints are based on physical laws, and do not make use of unknown parameters. Here, we show that the network structure (i.e. the stoichiometric matrix) alone provides a system of constraints on the fluxes in a biochemical network which are feasible according to both mass balance and the laws of thermodynamics. A realistic example shows that these constraints can be sufficient for deriving unambiguous, biologically meaningful results. The thermodynamic constraints are obtained by comparing of the sign pattern of the flux vector to the sign patterns of the cycles of the internal cycle space via connection between stoichiometric network theory (SNT) and the mathematical theory of oriented matroids.

Energy Metabolism↗
PubMed2005

Active transport: a kinetic description based on thermodynamic grounds.

We show that active transport processes in biological systems can be understood through a local equilibrium description formulated at the mesoscale, the scale to describe stochastic process. This new approach uses the method established by nonequilibrium thermodynamics to account for the irreversible processes occurring at this scale and provides nonlinear kinetic equations for the rates in terms of the driving forces. The results show that the application domain of nonequilibrium thermodynamics method to biological systems goes beyond the linear domain. A model for transport of Ca2+ by the Ca2+-ATPases, nonlinear way. Our results unify thermodynamic and kinetic descriptions, thereby opening new perspectives in the study of different transport phenomena in biological systems.

Animals↗
PubMed2005

Applying a neural network to predict the thermodynamic parameters for an expanded nearest-neighbor model.

Predicting the secondary and tertiary structure of RNAs largely depends on our capabilities in estimating the thermodynamics of RNA duplexes. In this work, an expanded nearest-neighbor model, designated INN-48, is established. The thermodynamic parameters of this model are predicted using both multiple linear regression analysis and neural network analysis. It is suggested that due to the increase in the number of parameters and the insufficiency of the existing data, neural network analysis results in more reliable predictions. Furthermore, it is suggested that INN-48 can be used to estimate the thermodynamics of RNA duplex formation for longer sequences, whereas INN-HB, the previous model on which INN-48 is based, can be used for short sequences.

Animals↗
PubMed2002

Thermodynamics of drug-DNA interactions.

Many anticancer, antibiotic, and antiviral drugs exert their primary biological effects by reversibly interacting with nucleic acids. Therefore, these biomolecules represent a major target in drug development strategies designed to produce next generation therapeutics for diseases such as cancer. In order to improve the clinical efficacy of existing drugs and also to design new ones it is necessary to understand the molecular basis of drug-DNA interactions in structural, thermodynamic, and kinetic detail. The past decade has witnessed an increase in the number of rigorous biophysical studies of drug-DNA systems and considerable knowledge has been gained in the energetics of these binding reactions. This is, in part, due to the increased availability of high-sensitivity calorimetric techniques, which have allowed the thermodynamics of drug-DNA interactions to be probed directly and accurately. The focus of this article is to review thermodynamic approaches to examining drug-DNA recognition. Specifically, an overview of a recently developed method of analysis that dissects the binding free energy of these reactions into five component terms is presented. The results of applying this analysis to the DNA binding interactions of both minor groove drugs and intercalators are discussed. The solvent water plays a key role in nucleic acid structure and consequently in the binding of ligands to these biomolecules. Any rational approach to DNA-targeted drug design requires an understanding of how water participates in recognition and binding events. Recent studies examining hydration changes that accompany DNA binding by intercalators will be reviewed. Finally some aspects of cooperativity in drug-DNA interactions are described and the importance of considering cooperative effects when examining these reactions is highlighted.

Animals↗
PubMed2003

Thermodynamics of the reduction of NADP with 2-propanol catalyzed by an NADP-dependent alcohol dehydrogenase.

The apparent equilibrium constant of the biochemical reaction, 2-propanol+NADP(ox) = acetone+NADP(red), was determined at I = 0.25 M over a wide range of pH (5.63 to 8.02) and temperature (5 to 40 degrees C). The reaction was catalyzed by an NADP-dependent alcohol dehydrogenase. The results were used to calculate thermodynamic quantities for the chemical (ionic) reference reaction: 2-propanol+NADP(ox)(3-) = acetone+NADP(red)(4-)+H(+). The thermodynamic quantities for this reference reaction are as follows: equilibrium constant K = (5.98+/-0.46) x 10(-10); standard molar Gibbs energy change Delta(r)G(0) = (52.65+/-0.19) kJmol(-1); standard molar enthalpy change Delta(r)H(0) = (38.9+/-0.6) kJmol(-1); and standard molar entropy change Delta(r)S(0) = -(46.1+/-2.2)J K(-1)mol(-1). All of these results pertain to 25 degrees C (298.15 K) and I = 0. The results also lead, in conjunction with tabulated thermodynamic quantities, to the standard electromotive force E(0) = -0.140 V for the reduction of NADP(ox)(3-) to NADP(red)(4-).

2-Propanol↗
PubMed2002

Monitoring the kinetics and thermodynamics of interfacial enzymatic catalysis by differential scanning calorimetry.

Using phase transition profile as an indicator of thermodynamic property and phase transition heat as the second indicator of the percentage of substrates unhydrolyzed, differential scanning calorimetry has been used to observe in detail the kinetics and thermodynamics of phospholipase A(2)-catalyzed 1,2-dipalmitoyl-sn-glycero-3-phosphocholine large unilamellar vesicle (LUV) hydrolysis. Phase transition profiles show that the original LUV almost completely changes into a novel aggregate at the end of the latency, followed by an abrupt activation of the reaction. The phase transition profiles are asymmetric between the heating and cooling curves, indicating a thermodynamic mesostatic property of the system. The reaction in activated phase follows a single first-order kinetics and all of the substrates in vesicles can be hydrolyzed. All these evidences indicate that the products and substrates can freely exchange between the outer and the inner layers of the vesicles and the membrane of the vesicle in the activated phase is permeable. This permeability favors the exchange of the substrates and products, thus, resulting in the activation of the fast reaction.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Hyperekplexia mutation of glycine receptors: decreased gating efficacy with altered binding thermodynamics.

[(3)H]Strychnine binding was studied to recombinant human alpha(1) and the hyperekplexia mutant alpha(1)R271L glycine receptors (GlyRs) transiently expressed in human embryonic kidney (HEK)-293 cell cultures at 0, 18 and 37 degrees. The alpha(1)R271L mutation did not affect the linear van't Hoff plots of the exothermic binding of the antagonist [3H]strychnine while it turned taurine into an antagonist with exothermic binding. The inhibition constants of the agonist glycine showed opposite temperature dependence on alpha(1) GlyRs, corresponding to endothermic binding driven by large entropic increases. The temperature dependence of displacement by the partial agonists taurine on alpha(1) GlyRs and glycine on alpha(1)R271L GlyRs was biphasic reflecting negative heat capacity changes, dehydration changes and/or a complex binding mechanism. The thermodynamic discrimination of efficacy is valid for native rat spinal and recombinant human GlyRs. The alpha(1)R271L mutation impairs the transduction mechanism and distorts gating of GlyRs. Thereby it reduces the potency and efficacy of agonists and affects their thermodynamic parameters of binding. The hyperekplexia mutation offers a model system to demonstrate the correlation among pathophysiology, gating efficacy and binding thermodynamics of GlyRs.

Amino Acid Motifs↗
PubMed2000

A theoretical model for the prediction of sequence-dependent nucleosome thermodynamic stability.

A theoretical model for predicting nucleosome thermodynamic stability in terms of DNA sequence is advanced. The model is based on a statistical mechanical approach, which allows the calculation of the canonical ensemble free energy involved in the competitive nucleosome reconstitution. It is based on the hypothesis that nucleosome stability mainly depends on the bending and twisting elastic energy to transform the DNA intrinsic superstructure into the nucleosomal structure. The ensemble average free energy is calculated starting from the intrinsic curvature, obtained by integrating the dinucleotide step deviations from the canonical B-DNA and expressed in terms of a Fourier series, in the framework of first-order elasticity. The sequence-dependent DNA flexibility is evaluated from the differential double helix thermodynamic stability. A large number of free-energy experimental data, obtained in different laboratories by competitive nucleosome reconstitution assays, are successfully compared to the theoretical results. They support the hypothesis that the stacking energies are the major factor in DNA rigidity and could be a measure of DNA stiffness. A dual role of DNA intrinsic curvature and flexibility emerges in the determination of nucleosome stability. The difference between the experimental and theoretical (elastic) nucleosome-reconstitution free energy for the whole pool of investigated DNAs suggests a significant role for the curvature-dependent DNA hydration and counterion interactions, which appear to destabilize nucleosomes in highly curved DNAs. This model represents an attempt to clarify the main features of the nucleosome thermodynamic stability in terms of physical-chemical parameters and suggests that in molecular systems with a large degree of complexity, the average molecular properties dominate over the local features, as in a statistical ensemble.

Base Sequence↗
PubMed2003

Molecular-level thermodynamic switch controls chemical equilibrium in sequence-specific hydrophobic interaction of 35 dipeptide pairs.

Applying the Planck-Benzinger methodology, the sequence-specific hydrophobic interactions of 35 dipeptide pairs were examined over a temperature range of 273-333 K, based on data reported by Nemethy and Scheraga in 1962. The hydrophobic interaction in these sequence-specific dipeptide pairs is highly similar in its thermodynamic behavior to that of other biological systems. The results imply that the negative Gibbs free energy change minimum at a well-defined stable temperature, , where the bound unavailable energy, TdeltaS(o) = 0, has its origin in the sequence-specific hydrophobic interactions, are highly dependent on details of molecular structure. Each case confirms the existence of a thermodynamic molecular switch wherein a change of sign in deltaCp(o)(T)(reaction) (change in specific heat capacity of reaction at constant pressure) leads to true negative minimum in the Gibbs free energy change of reaction, deltaG(o)(T)(reaction), and hence a maximum in the related equilibrium constant, K(eq). Indeed, all interacting biological systems examined to date by Chun using the Planck-Benzinger methodology have shown such a thermodynamic switch at the molecular level, suggesting its existence may be universal.

Amino Acid Sequence↗