Thermodynamics Of Structural Changes Research Articles

Exploring Conformational Landscapes Using Trap and Release Tandem Ion Mobility Spectrometry.

The dynamics and thermodynamics of structural changes in isolated glu-fibrinopeptide B (GluFib) were investigated by tandem ion mobility spectrometry (IMS). Doubly protonated GluFib2+ ions were first selected by IMS and then stored for a controlled duration in a thermalized ion trap. Temperature-induced conformational changes were finally monitored by IMS as a function of trapping time. Based on this procedure, isomerization rates and equilibrium populations of the different conformers were determined as a function of temperature. We demonstrate that the measured thermodynamic quantities can be directly compared to simulated observables from ensemble molecular modeling based on appropriate order parameters. We obtained good qualitative agreement with replica-exchange molecular dynamics simulations based on the AMOEBA force field and processed using the weighted histogram analysis method. This suggests that the balance between Coulomb repulsion and optimal charge solvation is the main source of the observed conformational bistability. Our results emphasize the differences between the kinetically driven quasi-equilibrium distributions obtained after collisional activation and the thermodynamically driven distributions from the present equilibrium experiments due to entropic effects. As a consequence, our measurements not only allow straightforward determination of Arrhenius activation energies but also yield the relative enthalpy and entropy changes associated to a structural transition.

Reduction of the internal disulfide bond between Cys 38 and 83 switches the ligand migration pathway in cytoglobin

Despite the similar tertiary structure between cytoglobin (Cygb) and myoglobin, several structural features indicate a distinct mechanism of Cygb interactions with exogenous ligands. Here we present a spectroscopic investigation of the dynamics and thermodynamics of structural changes associated with the exogenous ligand migration between the solvent and the heme active site in Cygb with reduced and oxidized Cys 38 and Cys 83 side-chains (Cygbox and Cygbred, respectively). Photo-acoustic and transient absorption data show that disulfide bond formation alters the ligand migration pathway(s) as evident from the distinct geminate quantum yields (Φgem=0.35 for Cygbox and Φgem=0.63 for Cygbred) and rate constants for bimolecular CO rebinding. Moreover, ligand escape from the protein matrix is fast (<40ns) and coupled with an enthalpy change of 18±2kcalmol−1 in Cygbred, whereas the disulfide bridge formation promotes a biphasic ligand escape associated with an overall enthalpy change of 9±4kcalmol−1. These results demonstrate that the disulfide bond connecting helix E and helix B modulates the conformational dynamics in Cygb including the size and energy barrier between the internal hydrophobic sites. Based on the comparison of the thermodynamic profiles for CO photo-dissociation from Cygb, myoglobin, and neuroglobin we propose that in Cygbred the photo-dissociated ligand escapes through the hydrophobic tunnel, whereas the CO preferably migrates through the His64 gate in Cygbox suggesting that Cygb's physiological role may vary in response to intracellular redox conditions.

Kinetics and Thermodynamics of the Rate-Limiting Conformational Change in the Actomyosin V Mechanochemical Cycle

We used FRET to examine the kinetics and thermodynamics of structural changes associated with ADP release in myosin V, which is thought to be a strain-sensitive step in many muscle and non-muscle myosins. We also explored essential dynamics using FIRST/FRODA starting with three different myosin V X-ray crystal structures to examine intrinsic flexibility and correlated motions. Our steady-state and time-resolved FRET analysis demonstrates a temperature-dependent reversible conformational change in the nucleotide-binding pocket (NBP). Our kinetic results demonstrate that the NBP goes from a closed to an open conformation prior to the release of ADP, while the actin-binding cleft remains closed. Interestingly, we find that the temperature dependence of the maximum actin-activated myosin V ATPase rate is similar to the pocket opening step, demonstrating that this is the rate-limiting structural transition in the ATPase cycle. Thermodynamic analysis demonstrates that the transition from the open to closed NBP conformation is unfavorable because of a decrease in entropy. The intrinsic flexibility analysis is consistent with conformational entropy playing a role in this transition as the MV.ADP structure is highly flexible compared to the MV.APO structure. Our experimental and modeling studies support the conclusion of a novel post-power-stroke actomyosin.ADP state in which the NBP and actin-binding cleft are closed. The novel state may be important for strain sensitivity as the transition from the closed to open NBP conformation may be altered by lever arm position.

Thermodynamics of Structural Changes in Liquid Ge–Te Alloys Around the Eutectic Composition: Specific Heat Measurements and Thermodynamic Stability

We have obtained the specific heat, C p , of liquid Ge–Te alloys around the eutectic composition (15 at.% Ge) and alloys up to 50 at.% Ge by combining the data obtained by modulation and adiabatic calorimetries. The results cover a wide temperature range from deeply undercooled state to 800°C. A very pronounced peak of C p was observed for Te and alloys up to 20 at.% Ge. The peak position of C p takes a maximum around the eutectic composition where the peak width becomes narrowest. Using a new thermodynamic relation, we clarify a correlation between the thermodynamic stability and structural changes in the liquid Ge–Te system.

Thermodynamic Evidence for Structural Changes in Liquid CdSb

The specific heat, molar volume, and sound velocity have been measured to investigate the thermodynamics of structural changes in liquid CdSb, from which the volume expansion coefficient and isothermal compressibility have also been deduced. These thermodynamic functions show unusually large temperature dependence around the melting point. It is shown that the Ehrenfest's relations in an extended form are satisfied, which gives strong support to chemical clusters in the liquid CdSb which dissociates with raising temperature.

The thermodynamics of structural changes in the liquid sulphur-tellurium system: compressibility and Ehrenfest's relations

The velocity of sound in liquid sulphur-tellurium (S-Te) has been measured to investigate structural changes induced by raising the temperature. The sound velocity in a Te-rich alloy as a function of temperature shows a peaked minimum, which shifts to higher temperatures with increasing S content. The results have been used to deduce the isothermal compressibility. It has been shown that Ehrenfest's relations are satisfied among the temperature dependences of the isothermal compressibility, constant-pressure specific heat and volume expansion coefficient. The relations also explain the initial slope of the polymerization line in the pressure-temperature diagram for liquid S.