Thermodynamic functions of conformational changes: conformational network of glycine diamide folding, entropy lowering, and informational accumulation

A refined grid of a conformational potential energy surface (PES) and a conformational entropy surface for glycine diamide was generated by ab initio molecular computations. The possible network of reaction paths was recognized in terms of the linear combinations of internal coordinates corresponding to conrotatory and disrotatory modes of motions. Such a Woodward-Hoffmann-like path selection principle was detected for the folding of this peptide from extended to some virtually cyclic structure. It seemed reasonable to assume that this principle (or its generalized form) might be applicable to protein folding. A reaction path network was projected on the potential energy, and a continuous entropy surface was constructed under the condition of reduced dimensionality. The low entropy of the folded conformation indicated an information accumulation between 326% and 1414% with respect to the fully extended or unfolded structure. It is found that the location of existing and 'latent' critical points on the surface is revealed by the extrema and inflection points of the entropy curve.     

Conformational entropy of a pseudoknot polymer

The thermodynamics and kinetics of ABAB pseudoknot formation owing to reversible intrachain reactions are investigated for a flexible polymer based on the off-lattice Monte Carlo simulations. The polymer is made of N hard spheres tethered by inextensible bonds and consists of two reactive pairs AA and BB with binding energies -epsilon1 and -epsilon2, respectively, and three loop lengths (l1, l2, and l3). Although two intermediate states, loops A and B, may be formed, the folding path goes mainly through the intermediate loop whose free energy reduction associated with coil-to-loop crossover is greater. The conformational entropy loss is found to follow DeltaS=alpha ln N+G, where alpha approximately 2.48 for coil-loop crossover and alpha approximately 2.43 for loop-pseudoknot crossover. The constant G depends on the three loop lengths and the two end-to-reactive site lengths (L1 and L2). For a given total loop length, G is maximum when the three loop lengths are equal (l1=l2=l3). When l1=l3, the entropy loss is minimum if l2=0. However, the condition l1 not equal l3 makes G even smaller. This consequence indicates that asymmetry in loop lengths is thermodynamically favorable and this fact is consistent with observations of pseudoknotted RNA structures.     

Shannon information entropy of fractional occupation probability as an electron correlation measure in atoms and molecules

A new method to determine electron correlation energy is presented for atoms and molecules. This method is based on Shannon information entropy that is obtained by fractional occupation probabilities of natural atomic orbitals. It is indicated that the Shannon entropy increases as the number of electrons increases and thus can be considered as a possible measure for the electron correlation in atomic and molecular systems. For neutral atoms and singly charged positive ions we proposed an expression for correlation energy with explicit dependence on the Shannon entropy and atomic number. The obtained correlation energies have been used to compute the first ionization potentials of the ground state of the main group elements from hydrogen through krypton. The calculated ionization potentials are in reasonably good agreement with their corresponding experimental values.We also developed the additivity scheme to find a connection between Shannon entropy and molecular correlation energy. The estimated molecular correlation energies show an excellent agreement with those obtained by elaborate G3 method with R² = 0.990.     

Hydrophobic interaction chromatography of proteins: Thermodynamic analysis of conformational changes

For BSA and β-lactoglobulin adsorption to hydrophobic interaction chromatography (HIC) stationary phases leads to conformational changes. In order to study the enthalpy (ΔH_ads), entropy (ΔS_ads), free energy (ΔG_ads) and heat capacity (Δc_p,ads) changes associated with adsorption we evaluated chromatographic data by the non-linear van’t Hoff model. Additionally, we performed isothermal titration calorimetry (ITC) experiments. van’t Hoff analysis revealed that a temperature raise from 278 to 308 K increasingly favoured adsorption seen by a decrease of ΔG_ads from −12.9 to −20.5 kJ/mol for BSA and from −6.6 to −13.2 kJ/mol for β-lactoglobulin. Δc_p,ads values were positive at 1.2 m (NH₄)₂SO₄ and negative at 0.7 m (NH₄)₂SO₄. Positive Δc_p,ads values imply hydration of apolar groups and protein unfolding. These results further corroborate conformational changes upon adsorption and their dependence on mobile phase (NH₄)₂SO₄ concentration. ITC measurements showed that ΔH_ads is dependent on surface coverage already at very low loadings. Discrepancies between ΔH_ads determined by van’t Hoff analysis and ITC were observed. We explain this with protein conformational changes upon adsorption which are not accounted for by van’t Hoff analysis.     

Treating entropy and conformational changes in implicit solvent simulations of small molecules

Implicit solvent models are increasingly popular for estimating aqueous solvation (hydration) free energies in molecular simulations and other applications. In many cases, parameters for these models are derived to reproduce experimental values for small molecule hydration free energies. Often, these hydration free energies are computed for a single solute conformation, neglecting solute conformational changes upon solvation. Here, we incorporate these effects using alchemical free energy methods. We find significant errors when hydration free energies are estimated using only a single solute conformation, even for relatively small, simple, rigid solutes. For example, we find conformational entropy (TDeltaS) changes of up to 2.3 kcal/mol upon hydration. Interestingly, these changes in conformational entropy correlate poorly (R2 = 0.03) with the number of rotatable bonds. The present study illustrates that implicit solvent modeling can be improved by eliminating the approximation that solutes are rigid.     

Gold nanoparticles as a colorimetric sensor for protein conformational changes

Spherical gold nanoparticles and flat gold films are prepared in which yeast iso-1-cytochrome c (Cyt c) is covalently bound to the gold surface by a thiol group in the cystein 102 residue. Upon exposure to solutions of different pH, bound Cyt c unfolds at low pH and refolds at high pH. This conformational change causes measurable shifts in the color of the coated nanoparticle solutions detected by UV-VIS absorption spectroscopy and in the refractive index (RI) of the flat gold films detected by surface plasmon resonance (SPR) spectroscopy. Both experiments demonstrate the same trend with pH, suggesting the use of protein-covered gold nanoparticles as a simple colorimetric sensor for conformational change.     

Thermodynamic functions of a morse oscillator

The partition function Q, entropy S and heat capacity C of a Morse oscillator are numerically evaluated from its overtone vibrational spectrum for typical values of the experimentally accesible fundamental frequency v and dissociation energy D. We show that significant departures from limiting harmonic oscillator values are to be expected for shallow potential wells.     

Conformational changes in beta-endorphin as studied by electrospray ionization mass spectrometry.

Because of a wide range of physiological functions, the structure of beta-endorphin (BE) is of great interest. In this study, conformational changes in BE induced by methanol are explored with electrospray ionization-mass spectrometry (ESI-MS). Differences in the charge-state distribution (CSD) and the extent of hydrogen/deuterium (H/D) exchange were used to monitor the conformational changes. The latter experiments were conducted via time-resolved ESI-MS in a continuous-flow apparatus. Both these techniques demonstrate that BE exists in a random coil open structure in aqueous media, but it acquires a more compact conformation with increased concentration of methanol. The H/D exchange experiments reveal that BE forms 61% alpha-helix in mixed solvents.     

Conformational analysis—CI : The gauche-hydrogen interaction as the basis of conformational analysis

It is concluded that the gauche-butane interaction which is one of the cornerstones of conformational analysis has been incorrectly interpreted as to origin, and that the gauche relationship between methyl (or methylene) groups is not the cause of the relative instability of gauche conformations. Rather, the gauche interactions between vicinal-2,3-hydrogens are mainly responsible. By the same taken, a substituent on a cyclohexane ring should not be said to have a preference for the equatorial position. Rather, the tertiary hydrogen has an energetic preference for an axial position, which leaves the substituent in the equatorial position by default. Several poorly understood phenomena are better interpreted on this basis.     

Wide-angle X-ray solution scattering as a probe of ligand-induced conformational changes in proteins

A chemical genetics approach to functional analysis of gene products utilizes high-throughput target-based screens of compound libraries to identify ligands that modulate the activity of proteins of interest. Candidates are further screened using functional assays designed specifically for the protein--and function--of interest, suffering from the need to customize the assay to each protein. An alternative strategy is to utilize a probe to detect the structural changes that usually accompany binding of a functional ligand. Wide-angle X-ray scattering from proteins provides a means to identify a broad range of ligand-induced changes in secondary, tertiary, and quaternary structure. The speed and accuracy of data acquisition, combined with the label-free targets and binding conditions achievable, indicate that WAXS is well suited as a moderate-throughput assay in the detection and analysis of protein-ligand interactions.     

Thermodynamic functions of proton ionisation of 1-and 2-naphthol

Thermodynamic acidity constants of 1-naphthol have been measured spectrophotometrically over the temperature range 5–60° and those of 2-naphthol over the temperature range 5–50°. The thermodynamic functions of ionisation, ΔG⁰₂₅, ΔH⁰₂₅ and ΔCp⁰₂₅ have been calculated for both acids.     

Impedance spectroscopy of reactive polymers. 5. Impedance as a measure of chemical and physical changes in glass formers

A study was conducted aimed at establishing the nature of chemical and physical phenomena in polymeric and nonpolymeric glass formers that can be observed by impedance measurements. Various systems were investigated that undergo a temporal evolution of structure as a result of chemical reactions and physical processes such as crystallization, vitrification, or phase separation. Distinct and systematic changes in impedance during crystallization and vitrification confirmed that these events could be monitored by impedance spectroscopy. Of particular interest was the potential use of impedance measurements in detecting gelation in crosslinking polymers. It was shown that the experimentally observed “knee” in imaginary impedance during reaction shifts with frequency and, hence, cannot be used to measure gelation. But a new insight at the molecular level was obtained by employing a novel experimental approach based on simultaneous dielectric-infrared measurements. Evidence was generated to support the formation of a hydrogen-bonded complex in the vicinity of gel point in polymer networks, which affords a vehicle for the migration of intrinsic charges and provides a contribution to the overall conductivity. This finding should be explored further because it suggests the possibility of correlating dielectric response with gelation. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36: 641–653, 1998     

trans-2-Aminocyclohexanol as a pH-sensitive conformational switch in lipid amphiphiles

Protonation-induced conformational change of lipid tails is reported as a novel strategy to render pH-sensitive lipid amphiphiles and lipid colloids.     

Thermodynamic and conformational properties of polystyrene. III. Dilute solution studies on branched polymers

Light-scattering and viscometric measurements on dilute solutions of five branched polystyrene polymers are reported. The data include studies in decalin as a function of temperature, including the theta temperature, and in toluene. The results for the radius of gyration and the second virial coefficient are not in accord with the two parameter random-flight model. Possible causes of this descrepancy are considered. It is shown that the intrinsic viscosity of branched chains is not uniquely determined by the radius of gyration.