Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “THERMODYNAMICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2005

Measurements of binding thermodynamics in drug discovery.

Thermodynamics governs the process of biomolecular recognition. The steps of characterizing, understanding and exploiting binding thermodynamics have the potential to contribute to an improved rational drug design process that is more robust and reliable. It is only relatively recently that instrumentation capable of direct and full thermodynamic characterization has been improved, giving impetus to the application of thermodynamic measurements in drug discovery. This review highlights current instruments and methods that can be employed to measure binding thermodynamics and their use in studies of biomolecular recognition and drug discovery.

Calorimetry↗
PubMed1999

Investigations into the thermodynamics of polypeptide interaction with nonpolar ligands.

In this paper, we describe a general procedure to evaluate the thermodynamics of the interaction between polypeptides and hydrophobic ligands in the presence of aquo-organic solvent mixtures. These studies address experimental requirements for the determination of the linear free energy relationships, derivation of partition coefficients or other extrathermodynamic parameters such as contact areas, or assessment of the conformational changes that may occur when polypeptides or proteins interact with immobilized nonpolar ligands. Not unexpectedly from thermodynamic arguments, the trends and magnitudes of free energy parameters, such as the enthalpy of association, as previously derived in many studies from gradient elution reversed-phase high-performance liquid chromatographic (RP-HPLC) measurements are often different from the data for the same parameters derived from equilibrium binding or microcalorimetric determinations. To reconcile these divergencies and to more closely examine the thermodynamic basis of the interaction of polypeptides with nonpolar ligands, the dependency of the logarithmic capacity factor, ln k', on temperature, T, for several polypeptides (bombesin, beta-endorphin, glucagon) have been investigated using a n-butylsilica and acetonitrile-water or methanol-water mixtures of defined solvent compositions. With low-pH, acetonitrile-water mixtures, the van't Hoff plots, i.e., the plots of ln k' versus 1/T, were nonlinear over the range of T = 278-358 K, although within a narrow temperature range, e.g., from T = 278-308 K, the experimental data for these polypeptides could be approximated by a linear relationship. This nonclassical van't Hoff behavior was associated with interactive processes that involved temperature-dependent enthalpic, entropic, and heat capacity changes. In contrast, with low-pH, methanol-water mixtures, the van't Hoff plots showed dependencies that were essentially linear over the range of T = 278-358 K. The slopes of the van't Hoff plots with acetonitrile-water and methanol-water mixtures at a defined T value and solvent composition were significantly larger than those found for the corresponding experiments carried out under gradient elution RP-HPLC conditions. From these plots of ln k' versus 1/T, the changes in the apparent enthalpy of association (delta H++assoc) and the apparent entropy of association (delta S++assoc) for the interaction of these polypeptides with the solvated n-butyl ligands at different T and solvent compositions have been determined. For these polypeptides, both delta H++assoc and delta S++assoc exhibited linear dependencies on the volume fraction, phi, of the organic solvent over a narrow range of T, but the slopes of these plots were dependent on the T range examined. The dependencies of the slope term, S, and the intercept term, ln ko, derived from the plots of ln k' versus phi as a function of T, have also been investigated. A new relationship linking the S values with delta H++assoc and delta S++assoc as a function of T and phi has been derived and validated. In addition, the relationship between S, delta H++assoc, delta S++assoc, the apparent change in heat capacity, delta C++assoc, and the accessible surface area, delta Atot, of these polypeptides has been examined, thus providing a linkage of these thermodynamic and extrathermodynamic parameters to the partition coefficient, P, and the molecular properties of these polypeptides. The results confirm that entropy-enthalpy compensation effects participate in the interaction of polypeptides with hydrophobic ligands. This investigation has confirmed that the use of solvent-water mixtures of defined composition, rather than the more convenient practice of using gradient elution methods, is essential if thermodynamically consistent values of the binding affinities and partition coefficients are to be quantitatively derived. (ABSTRACT TRUNCATED)

Acetonitriles↗
PubMed1993

Thermodynamic characterization of daunomycin-DNA interactions: comparison of complete binding profiles for a series of DNA host duplexes.

Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (delta G degree, delta H degree, and delta S degree) for the complexation of daunomycin to a series of 10 polymeric DNA duplexes. We find the resulting drug binding data to be sensitive to the base composition and sequence of the host duplex, with the binding free energies ranging from -7.5 to -10.8 kcal/mol of bound drug and the binding enthalpies ranging from +4.11 to -10.76 kcal/mol of bound drug at 25 degrees C. The smaller range in the free energy term reflects the impact of large enthalpy-entropy compensations. We observe that the three synthetic duplexes which exhibit the highest daunomycin binding affinities all contain GC (or IC) base pairs as part of alternating purine/pyrimidine sequence motifs, with these high binding affinities being strongly enthalpy driven at 25 degrees C. Specific comparisons between the binding profiles for daunomycin complexation with select pairs of host duplexes lead to the following observations: (1) The presence or absence of a major-groove methyl group does not alter daunomycin binding thermodynamics. (2) The presence or absence of a minor-groove amino group does alter daunomycin binding thermodynamics. (3) Duplexes with different base compositions but identical minor-groove functionality exhibit similar daunomycin binding thermodynamics. (4) Homopolymeric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy-entropy compensations in their daunomycin binding profiles. We propose interpretations of these and other features of our thermodynamic data in terms of specific daunomycin-DNA interactions deduced from available structural data.

Base Composition↗
PubMed2002

The GAAA tetraloop-receptor interaction contributes differentially to folding thermodynamics and kinetics for the P4-P6 RNA domain.

Tetraloops with the generic sequence GNRA are commonly found in RNA secondary structure, and interactions of such tetraloops with "receptors" elsewhere in RNA play important roles in RNA structure and folding. However, the contributions of tetraloop-receptor interactions specifically to the kinetics of RNA tertiary folding, rather than the thermodynamics of maintaining tertiary structure once folded, have not been reported. Here we investigate the role of the key GAAA tetraloop-receptor motif in folding of the P4-P6 domain of the Tetrahymena group I intron RNA. Insertions of one or more nucleotides into the tetraloop significantly disrupt the thermodynamics of tertiary folding; single-nucleotide insertions shift the folding free energy by 2-4 kcal/mol (DeltaDeltaG(o)'). The folding kinetics of several modified P4-P6 domains were determined by stopped-flow fluorescence spectroscopy, using an internally incorporated pyrene residue as the chromophore. In contrast to the thermodynamic results, the kinetics of Mg(2+)-induced folding were barely affected by the tetraloop modifications, with a DeltaDeltaG(++) of 0.2-0.4 kcal/mol and a Phi value (ratio of the kinetic and thermodynamic contributions) of <0.1. These data indicate an early transition state for folding of P4-P6 with respect to forming the tetraloop-receptor contact, consistent with previous results for modifications elsewhere in P4-P6. We conclude that the GAAA tetraloop-receptor motif contributes little to the stabilization of the transition state for Mg(2+)-induced P4-P6 folding. Rather, the tetraloop-receptor motif acts to clamp the RNA once folding has occurred. This is the first report to correlate the kinetic and thermodynamic contributions of an important RNA tertiary motif, the GNRA tetraloop-receptor. The results are related to possible models for the Mg(2+)-induced folding of the P4-P6 RNA, including a model invoking rapid nonspecific electrostatic collapse.

Adenine↗
PubMed2004

Thermodynamics of aminoglycoside binding to aminoglycoside-3'-phosphotransferase IIIa studied by isothermal titration calorimetry.

The aminoglycoside-3'-phosphotransferase IIIa [APH(3')-IIIa] phosphorylates aminoglycoside antibiotics and renders them ineffective against bacteria. APH(3')-IIIa is the most promiscuous aminoglycoside phosphotransferase enzyme, and it modifies more than 10 different aminoglycoside antibiotics. A wealth of information exists about the enzyme; however, thermodynamic properties of enzyme-aminoglycoside complexes are still not known. This study describes the determination of the thermodynamic parameters of the binary enzyme-aminoglycoside and the ternary enzyme-metal-ATP-aminoglycoside complexes of structurally related aminoglycosides using isothermal titration calorimetry. Formation of the binary enzyme-aminoglycoside complexes is enthalpically driven and exhibits a strongly disfavored entropic contribution. Formation of the ternary enzyme-metal-ATP-aminoglycoside complexes yields much smaller negative DeltaH values and more favorable entropic contributions. The presence of metal-ATP generally increases the affinity of aminoglycosides to the enzyme. This is consistent with the kinetic mechanism of the enzyme in which ordered binding of substrates occurs. However, the observed DeltaH values neither correlate with kinetic parameters k(cat), K(m), and k(cat)/K(m) nor correlate with the molecular size of the substrates. Comparison of the thermodynamic properties of the complexes formed by structurally similar aminoglycosides indicated that the 2'- and the 6'-amino groups of the substrates are involved in binding to the enzyme. Thermodynamic properties of the complexes formed by aminoglycosides differing only at the 3'-hydroxyl group suggested that the absence of this group does not alter the thermodynamic parameters of the ternary APH(3')-IIIa-metal-ATP-aminoglycoside complex. Our results also indicate that protonation of ligand and protein ionizable groups is coupled to the complex formation between aminoglycosides and APH(3')-IIIa. Comparison of DeltaH values for different aminoglycoside-enzyme complexes indicates that enzyme and substrates undergo significant conformational changes in complex formation.

Adenosine Triphosphate↗
PubMed1998

Thermodynamic analysis of an RNA combinatorial library contained in a short hairpin.

Prediction of nucleic acid structure from sequence requires thermodynamic parameters for a variety of motifs, many of which are complex and consist of a large number of possible sequence combinations. Here we report an experimental approach for identifying the stable and unstable members of an RNA combinatorial library. Short model RNA hairpins consisting of 13 base pairs (bp) flanked by primer binding sites are constructed and separated according to their relative thermodynamic stabilities using temperature gradient gel electrophoresis (TGGE). Partially denaturing TGGE is carried out with potassium chloride, sodium chloride, or magnesium chloride salts in the gel. The TMs of model hairpins can be tuned by adjusting the concentration of urea in the gel while maintaining the correct order of stabilities for the hairpins. Mixtures of RNAs differing by a single Watson-Crick base pair are resolved according to their relative thermodynamic stabilities, as are mixtures of GC or AU base pair transversions differing in DeltaG degrees37 by only 0.3-0.5 kcal/mol. In addition, a simple combinatorial library with one position of randomization opposite a guanosine is prepared and separated into its four members by parallel and perpendicular TGGE. The order of thermodynamic stabilities for the library determined by TGGE is shown to be the same when assayed by UV-melting experiments. Analysis of the thermodynamics of folding of combinatorial libraries is general and may be applied to a wide variety of complex nucleic acid secondary and tertiary motifs in order to identify the stable and unstable members.

Base Sequence↗
PubMed1999

Isolation and characterization of thermodynamically stable and unstable RNA hairpins from a triloop combinatorial library.

Hairpins are the most common elements of RNA secondary structure, playing important roles in RNA tertiary architecture and forming protein binding sites. Triloops are common in a variety of naturally occurring RNA hairpins, but little is known about their thermodynamic stability. Reported here are the sequences and thermodynamic parameters for a variety of stable and unstable triloop hairpins. Temperature gradient gel electrophoresis (TGGE) can be used to separate a simple RNA combinatorial library based on thermal stability [Bevilacqua, J. M., and Bevilacqua, P. C. (1998) Biochemistry 45, 15877-15884]. Here we introduce the application of TGGE to separating and analyzing a complex RNA combinatorial library based on thermal stability, using an RNA triloop library. Several rounds of in vitro selection of an RNA triloop library were carried out using TGGE, and preferences for exceptionally stable and unstable closing base pairs and loop sequences were identified. For stable hairpins, the most common closing base pair is CG, and U-rich loop sequences are preferred. Closing base pairs of GC and UA result in moderately stable hairpins when combined with a stable loop sequence. For unstable hairpins, the most common closing base pairs are AU and UG, and U-rich loop sequences are no longer preferred. In general, the contributions of the closing base pair and loop sequence to overall hairpin stability appear to be additive. Thermodynamic parameters for individual hairpins determined by UV melting are generally consistent with outcomes from selection experiments, with hairpins containing a CG closing base pair having a DeltaDeltaG degrees (37) 2.1-2.5 kcal/mol more favorable than hairpins with other closing base pairs. Sequences and thermodynamic rules for triloop hairpins should aid in RNA structure prediction and determination of whether naturally occurring triloop hairpins are thermodynamically stable.

Base Composition↗
PubMed2005

Thermodynamic analysis of arsenic methylation.

The Challenger mechanism for the methylation of arsenic is a repeating sequence of a two-electron reduction of pentavalent arsenic As(V) species to trivalent arsenic As(III) species followed by a methylation-oxidation reaction forming the successive methyl As(V) species. This unusual oxidation-reduction sequence prompted an examination of the thermodynamics of these reactions. Quantum chemical methods are employed to estimate the thermodynamic parameters for the methyl arsenic species. The sequence is thermodynamically favored at neutral pH for redox potentials with pe < 0 and methyl cation activities pCH3+ < -3 to -7 depending on the precise situation analyzed. The observed distribution of methyl arsenic species in human urine, which is remarkably constant across many studied populations, can be reproduced using an equilibrium model if the formation of TMA species is prevented. The estimated thermodynamic parameters are sufficiently accurate to evaluate questions of thermodynamic plausibility but not the precise details of speciation.

Arsenic↗
PubMed2005

Solvent control on the selective, nonselective, and absent response of a partially substituted lower rim calix(4)arene derivative for soft metal cations (mercury(II) and silver(I)). Structural and thermodynamic studies.

The solvent control on the ability of a partially substituted lower rim calix(4)arene derivative 5,11,17,23,tetra-tert-butyl[25,27-bis(hydroxy)-26,28-bis(ethylthioethoxy)]-calix(4)arene, 1 to host soft metal cations (Hg(II) and Ag(I)) is demonstrated through 1H NMR, electrochemical (conductance measurements), and thermodynamic characterization of the complexation process in a wide variety of solvents. Solvent-ligand interactions were assessed from 1H NMR measurements involving 1 and various solvents in CDCl3. Thus, the formation of a 1:1 1-CH3CN adduct is reported. As far as metal cations are concerned, depending on the medium their complexation with 1 was only observed for Hg(II) and Ag(I). Thus, in acetonitrile, 1 is more selective for Hg(II) relative to Ag(I) by a factor of 2.2 x 10(3). In methanol the selectivity is reversed to an extent that the affinity of 1 for Ag(I) is 1.4 x 10(3) higher than that for Hg(II). However, 1 is unable to recognize selectively these cations in N,N-dimethylformamide while in propylene carbonate the ability of 1 to interact with these cations is lost. An outstanding feature of thermodynamics emerges when an assessment is made of the ligand effect on the complexation of these cations and analogues calix(4)arene derivatives. Thus, in acetonitrile the thermodynamics of cation complexation by the hydrophilic cavity of a calix(4)arene containing mixed pendant groups is built up from thermodynamic data for the same process involving derivatives with common functionalities at the narrow rim. This is a unique example of the additive contribution of pendant arms in the field of thermodynamics of calixarene chemistry.

Acetonitriles↗
PubMed2005

The mesoscopic dynamics of thermodynamic systems.

Concepts of everyday use such as energy, heat, and temperature have acquired a precise meaning after the development of thermodynamics. Thermodynamics provides the basis for understanding how heat and work are related and the general rules that the macroscopic properties of systems at equilibrium follow. Outside equilibrium and away from macroscopic regimes, most of those rules cannot be applied directly. Here we present recent developments that extend the applicability of thermodynamic concepts deep into mesoscopic and irreversible regimes. We show how the probabilistic interpretation of thermodynamics together with probability conservation laws can be used to obtain Fokker-Planck equations for the relevant degrees of freedom. This approach provides a systematic method to obtain the stochastic dynamics of a system directly from its equilibrium properties. A wide variety of situations can be studied in this way, including many that were thought to be out of reach of thermodynamic theories, such as nonlinear transport in the presence of potential barriers, activated processes, slow relaxation phenomena, and basic processes in biomolecules, such as translocation and stretching.

Computer Simulation↗
PubMed2002

Temperature dependence of thermodynamic properties for DNA/DNA and RNA/DNA duplex formation.

A clear difference in the enthalpy changes derived from spectroscopic and calorimetric measurements has recently been shown. The exact interpretation of this deviation varied from study to study, but it was generally attributed to the non-two-state transition and heat capacity change. Although the temperature-dependent thermodynamics of the duplex formation was often implied, systemic and extensive studies have been lacking in universally assigning the appropriate thermodynamic parameter sets. In the present study, the 24 DNA/DNA and 41 RNA/DNA oligonucleotide duplexes, designed to avoid the formation of hairpin or slipped duplex structures and to limit the base pair length less than 12 bp, were selected to evaluate the heat capacity changes and temperature-dependent thermodynamic properties of duplex formation. Direct comparison reveals that the temperature-independent thermodynamic parameters could provide a reasonable approximation only when the temperature of interest has a small deviation from the mean melting temperature over the experimental range. The heat capacity changes depend on the base composition and sequences and are generally limited in the range of -160 to approximately -40 cal.mol-1.K-1 per base pair. In contrast to the enthalpy and entropy changes, the free energy change and melting temperature are relatively insensitive to the heat capacity change. Finally, the 16 NN-model free energy parameters and one helix initiation at physiological temperature were extracted from the temperature-dependent thermodynamic data of the 41 RNA/DNA hybrids.

Base Pairing↗
PubMed2000

Effects of food processing on the thermodynamic and nutritive value of foods: literature and database survey.

One of the goals of our society is to provide adequate nourishment for the general population of humans. In the strictness sense, the foodstuffs which we ingest are bundles of thermodynamic energy. In our post-industrial society, food producers provide society with the bioenergetic content of foods, while stabilizing the food in a non-perishable form that enables the consumer to access foods that are convenient and nutritious. As our modern society developed, the processing of foodstuffs increased to allow consumers flexibility in their choice in which foods to eat (based on nutritional content and amount of post-harvest processing). The thermodynamic energy content of foodstuffs is well documented in the literature by the use of bomb calorimetry measurements. Here, we determine the effects of processing (in most cases by the application of heat) on the thermodynamic energy content of foods in order to investigate the role of processing in daily nutritional needs. We also examine which processing procedures affect the nutritive quality (vitamin and mineral content) and critically assess the rational, advantages and disadvantages of additives to food. Finally, we discuss the role of endogenous enzymes in foods not only on the nutritive quality of the food but also on the freshness and flavor of the food. Our results show that a significant decrease in thermodynamic energy content occurs in fruits, vegetables, and meat products upon processing that is independent of water content. No significant change in energy content was observed in cereals, sugars, grains, fats and oils, and nuts. The vitamin content of most foods was most dramatically decreased by canning while smaller effects were observed upon blanching and freezing. We found that most food additives had very little effect on thermodynamic energy content due to their presence in minute quantities and that most were added to preserve the foodstuff or supplement its vitamin content. The endogenous food enzymes while aiding in digestibility of some foods (yogurt or grains) also helped some foods have a more palatable taste. Our conclusions are there is some scientific merit to the idea that enzymes in food can act synergistically with those in the human body to facilitate maximum nutritive value of foods.

Calorimetry↗
PubMed1987

Origins of netropsin binding affinity and specificity: correlations of thermodynamic and structural data.

We report complete thermodynamic profiles for netropsin binding to an oligomeric and to several polymeric DNA host duplexes. These data allow us to reach the following conclusions: netropsin binding by deep penetration into the minor groove is overwhelmingly enthalpy driven and exhibits a very high binding affinity (K approximately 10(9) at 25 degrees C); deep penetration into the minor groove is required to form those drug-DNA interactions responsible for the enthalpy-driven high binding affinity of netropsin; I-C base pairs form binding sites for netropsin that thermodynamically are equivalent to those formed by A-T base pairs; the positive binding entropies reflect entropic contributions from molecular events other than just water spine disruption; the thermodynamic binding data primarily reflect local netropsin-DNA interactions rather than long-range binding-induced conformational changes at regions distant from the binding site; the enhanced binding affinity associated with deep penetration of netropsin into the minor groove does not result from more favorable electrostatic interactions; the binding of netropsin to the central AATT core of the decamer duplex [d(GCGAATTCGC)]2 is thermodynamically modeled best by netropsin binding to the poly[d(AT)].poly[d(AT)] duplex rather than the poly(dA).poly(dT) duplex. We propose correlations between our thermodynamic data and specific molecular interactions defined by NMR and x-ray structural studies on similar and identical drug-DNA complexes.

Base Sequence↗
PubMed1989

Influence of abasic and anucleosidic sites on the stability, conformation, and melting behavior of a DNA duplex: correlations of thermodynamic and structural data.

We report a complete thermodynamic characterization of the impact of abasic and anucleosidic lesions on the stability, conformation, and melting behavior of a DNA duplex. The requisite thermodynamic data were obtained by using a combination of spectroscopic and calorimetric techniques to investigate helix-to-coil transitions in a family of DNA duplexes of the form d(CGCATGAGTACGC).d(GCGTACXCATGCG), where X corresponds to a thymidine residue in the parent Watson-Crick duplex and to an abasic or anucleosidic site in the modified duplexes. The data derived from these studies reveal that incorporation of an abasic site into a DNA duplex dramatically reduces the duplex stability, transition enthalpy, and transition entropy. The magnitudes of these lesion-induced effects are greater than one would expect based on simple nearest-neighbor considerations. Nearly identical thermodynamic data are obtained when the modified duplex contains an anucleosidic site rather than an abasic site. This observation suggests that the thermodynamic impact of these lesions primarily results from removal of the base rather than the sugar ring. Significantly, the melting cooperativities of the abasic and anucleosidic derivatives are identical with each other and with the corresponding unmodified Watson-Crick parent duplex. This result suggests that the phosphodiester backbone, rather than the base-sugar network, serves as the primary propagation path for the communication of cooperative melting effects. We propose molecular interpretations for the thermodynamic data based on the structural picture that has emerged from the NMR studies of Patel and coworkers on the same family of modified and unmodified DNA duplexes [Kalnik, M.W., Chang, C.-N., Grollman, A.P. & Patel, D.J. (1988) Biochemistry 27, 924-931].

Apurinic Acid↗
PubMed1998

Thermodynamics of binding of the core trimannoside of asparagine-linked carbohydrates and deoxy analogs to Dioclea grandiflora lectin.

The Man/Glc-specific seed lectin from Dioclea grandiflora (DGL) is a member of the Diocleinae subtribe that includes the jack bean lectin concanavalin A (ConA). Both DGL and ConA bind with high affinity to the "core" trimannoside moiety, 3, 6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, which is present in asparagine-linked carbohydrates. Recent hemagglutination inhibition studies suggest that DGL and ConA recognize similar epitopes of the trisaccharide but possess different binding specificities for complex carbohydrates (Gupta, D., Oscarson, S., Raju, T. S., Stanley, P., Toone, E. J., and Brewer, C. F. (1996) Eur. J. Biochem. 242, 320-326). In the present study, we have used isothermal titration microcalorimetry to determine the thermodynamics of binding of DGL to a complete set of monodeoxy analogs of the core trimannoside as well as a tetradeoxy analog. The thermodynamic data indicate that DGL recognizes the 2-, 3-, 4-, and 6-hydroxyl groups of the alpha(1,6) Man residue, the 3- and 4-hydroxyl group of the alpha(1, 3) Man residue, and the 2- and 4-hydroxyl groups of the central Man residue of the trimannoside. The thermodynamic data for the tetradeoxy analog lacking the 3- and 4-hydroxyl group of the alpha(1, 3) Man residue, and the 2- and 4-hydroxyl groups of the central Man residue of the trimannoside are consistent with the involvement of these hydroxyl groups in binding. While the overall pattern of data for DGL binding to the deoxy analogs is similar to that for ConA (Gupta, D., Dam, T. K., Oscarson, S., and Brewer, C. F. (1997) J. Biol. Chem. 272, 6388-6392), differences exist in the data for certain monodeoxy analogs binding to the two lectins. Differences are also observed in the thermodynamics of binding of DGL and ConA to a biantennary complex carbohydrate. In the following paper (Rozwarski, D. A., Swami, B. M., Brewer, C. F., and Sacchettini, J. C. (1998) J. Biol. Chem. 273, 32818-32825), the x-ray crystal structure of DGL complexed to the core trimannoside is presented, and a comparison is made of the thermodynamic binding data for DGL and ConA as well as the structures of their respective trimannoside complexes.

Asparagine↗
PubMed2001

Thermodynamic propensities of amino acids in the native state ensemble: implications for fold recognition.

An amino acid sequence, in the context of the solvent environment, contains all of the thermodynamic information necessary to encode a three-dimensional protein structure. To investigate the relationship between an amino acid sequence and its corresponding protein fold, a database of thermodynamic stability information was assembled that spanned 2951 residues from 44 nonhomologous proteins. This information was obtained using the COREX algorithm, which computes an ensemble-based description of the native state of a protein. It was observed that amino acid types partitioned unequally into high, medium, and low thermodynamic stability environments. Furthermore, these distributions were reproducible and were significantly different than those expected from random partitioning. To assess the structural importance of the distributions, simple fold-recognition experiments were performed based on a 3D-1D scoring matrix containing only COREX residue stability information. This procedure was able to recover amino acid sequences corresponding to correct target structures more effectively than scoring matrices derived from randomized data. High-scoring sequences were often aligned correctly with their corresponding target profiles, suggesting that calculated thermodynamic stability profiles have the potential to encode sequence information. As a control, identical fold-recognition experiments were performed on the same database of proteins using DSSP secondary structure information in the scoring matrix, instead of COREX residue stability information. The comparable performance of both approaches suggested that COREX residue stability information and secondary structure information could be of equivalent utility in more sophisticated fold-recognition techniques. The results of this work are a consequence of the idea that amino acid sequences fold not into single, rigidly stable structures but rather into thermodynamic ensembles best represented by a time-averaged structure.

Algorithms↗
PubMed2002

Thermodynamic environments in proteins: fundamental determinants of fold specificity.

To investigate the relationship between an amino acid sequence and its corresponding protein fold, a database of thermodynamic stability information was assembled as a function of residue type from 81 nonhomologous proteins. This information was obtained using the COREX algorithm, which computes an ensemble-based description of the native state of proteins. Dissection of the COREX stability constant into its fundamental energetic components resulted in 12 thermodynamic environments describing the tertiary architecture of protein folds. Because of the observation that residue types partitioned unequally between these environments, it was hypothesized that thermodynamic environments contained energetic information that connected sequence to fold. To test the significance of this hypothesis, the thermodynamic stability information was incorporated into a three-dimensional-to-one-dimensional scoring matrix, and simple fold recognition experiments were performed in a manner such that information about the fold target was never included in the scoring. For 60 out of 81 fold targets, the correct sequence for the target scored in the top 5% of 3858 decoy sequences, with Z-scores ranging from 1.76 to 12.23. Furthermore, a scoring matrix assembled from the residues of 40 nonhomologous all-alpha proteins was used to thread sequences against 12 nonhomologous all-beta protein targets. In 10 of 12 cases, sequences known to adopt the native all-beta structure scored in the top 5% of 3858 decoy sequences, with Z-scores ranging from 1.99 to 7.94. These results indicate that energetic information encoded by thermodynamic environments represents a fundamental property of proteins that underlies classifications based on secondary structure.

Algorithms↗
PubMed1987

Physico-chemical studies of micelle formation on sepia cartilage collagen solutions in acetate buffer and its interaction with ionic and nonionic micelles. Hydrodynamic and thermodynamic studies.

Sepia cartilage collagen (pepsin-extracted) in acetate buffer (pH = 2.98) forms micelles at a particular concentration below which they do not normally form. The critical micelle concentration (cmc) of the collagen was determined in buffer as well as in SDS, cetyltrimethylammonium bromide (CTAB) and Tween-80 micellar environments at different temperatures. Mutual interaction of collagen micelles with the ionic and nonionic micelles through the formation of the mixed micelle concept has also been found. The cmc of collagen decreased in the presence of SDS and Tween-80 micelles whereas it increased in the presence of CTAB micelles. This clearly suggests that the micelle formation of collagen is facilitated by the presence of SDS and Tween-80 and hindered by CTAB micelles. The various thermodynamic parameters were estimated from viscosity measurements and the transfer of collagen into the micelles of various surfactants and the reverse phenomenon was analyzed. This analysis has also been modelled conceptually as a different phase and the results have supported the above phenomenon. Our thermodynamic results are also able to predict the exact denaturation temperature as well as the structural order of water in the collagen in various environments. The hydrated volumes, Vh, of collagen in the above environments and intrinsic viscosity were also calculated. The low intrinsic viscosity, [eta], of collagen in an SDS environment compared to buffer and other surfactant environments suggested more workable systems in cosmetic and dermatological skin care preparations. The one and two-hydrogen-bonded models of this collagen in various environments have been analyzed. The calculated thermodynamic parameters varied with the concentration of collagen. The change of thermodynamic parameters from coil-coil to random-coil conformation upon denaturation of collagen were calculated from the amount of proline and hydroxyproline residues and compared with viscometric results. Thermodynamic results suggest that the stability of the collagen in the additive environments is in the following order: SDS greater than Tween-80 greater than buffer greater than CTAB.

Acetates↗