Search Results (6)

Because of the involvement of π-electron cyclic constituents in their side chains, the so-called aromatic residues give rise to a number of strong, narrow, and well-resolved lines spread over the middle wavenumber (1800–600 cm⁻¹) region of the Raman spectra of peptides and proteins. The number of characteristic aromatic markers increases with the structural complexity (Phe → Tyr → Trp), herein referred to as (F_i = 1, …, 6) in Phe, (Y_i = 1, …, 7) in Tyr, and (W_i = 1, …, 8) in Trp. Herein, we undertake an overview of these markers through the analysis of a representative data base gathered from the most structurally simple tripeptides, Gly-Xxx-Gly (where Xxx = Phe, Tyr, Trp). In this framework, off-resonance Raman spectra obtained from the aqueous samples of these tripeptides were jointly used with the structural and vibrational data collected from the density functional theory (DFT) calculations using the M062X hybrid functional and 6-311++G(d,p) atomic basis set. The conformation dependence of aromatic Raman markers was explored upon a representative set of 75 conformers, having five different backbone secondary structures (i.e., β-strand, polyproline-II, helix, classic, and inverse γ-turn), and plausible side chain rotamers. The hydration effects were considered upon using both implicit (polarizable solvent continuum) and explicit (minimal number of 5–7 water molecules) models. Raman spectra were calculated through a multiconformational approach based on the thermal (Boltzmann) average of the spectra arising from all calculated conformers. A subsequent discussion highlights the conformational landscape of conformers and the wavenumber dispersion of aromatic Raman markers. In particular, a new interpretation was proposed for the characteristic Raman doublets arising from Tyr (~850–830 cm⁻¹) and Trp (~1360–1340 cm⁻¹), definitely excluding the previously suggested Fermi-resonance-based assignment of these markers through the consideration of the interactions between the aromatic side chain and its adjacent peptide bonds. Full article

Natural gas hydrates (shortened as hydrates) are expected to be a prospective alternative to traditional fossil energies. The main strategy of exploring hydrates is achieved by dissociating solid hydrates into gas and water with the depressurization method. However, we have little knowledge on the changes in heat and energy, which are implicit essences compared with explicit temperature. Thus, this study for the first time investigates the evolutionary patterns of heat and energy during hydrate dissociation, by fully coupled thermal–hydraulic–mechanical–chemical modelling. A novel numerical technique (physics-based constrained conditions) is proposed to guarantee the stability and precision of the numerical computation. The classic Masuda’s experiment is used as a case study. Results show that the cumulative conduction heat tends to increase first and then decrease during the dissociation of hydrate, while the cumulative advection heat has the tendency to increase monotonically. External heat sources increase the energy, while phase change has a reduction effect on the change in energy. The role of conduction heat is minor, but the contribution of advection heat is considerable for the change in energy. Additionally, two implications are given for lab-scale experiments and in situ engineering from the perspective of energy. Our findings provide new insights into the mechanism of hydrate dissociation and are beneficial to the real-world engineering of hydrate exploration in terms of cost evaluation. Full article

Water molecules were easy to combine with organic molecules and embed into the lattice of solid molecules to form a hydrate. Compared with anhydrous compounds, a hydrate has completely different physical and chemical properties. In this paper, terahertz (THz) spectra of five nucleosides in the solid and liquid phases were studied experimentally by Fourier-transform infrared spectroscopy (FTIR) in the frequency of 0.5–9 THz. In addition, the lattice energy, geometric structure, and vibration spectrum of the molecular crystal of the nucleosides were analyzed theoretically by the generalized energy-based fragmentation approach under periodic boundary conditions (denoted as PBC-GEBF). Furthermore, different nucleoside molecular morphology (monomer, polymer, and crystal), solvent (implicit and explicit water), and temperature/theoretical model effect on the THz spectra were mainly investigated. It was found that in the low-frequency band, the vibrational modes were generally originated from the collective vibration of all molecules involved (more than 99% of them were vibration; only less than 1% of them were rotation and translation), which can reflect the molecular structure and spatial distribution of different substances. The Gibbs free energy of thymidine monomer, dimer, tetramer, and crystal was studied. It was found that the cell-stacking energy had the greatest influence on the spectrum, indicating that only the crystal structure constrained by the periodic boundary conditions could well describe the experimental results. In addition, hydrophobic forces dominated the formation of new chemical bonds and strong inter-molecular interactions; the free water had little contribution to the THz spectrum of nucleosides, while crystalline water had a great influence on the spectrum. Full article

For many years, we have devoted our research to the study of the thermodynamic properties of hydrophobic hydration processes in water, and we have proposed the Ergodic Algorithmic Model (EAM) for maintaining the thermodynamic properties of any hydrophobic hydration reaction at a constant pressure from the experimental determination of an equilibrium constant (or other potential functions) as a function of temperature. The model has been successfully validated by the statistical analysis of the information elements provided by the EAM model for about fifty compounds. The binding functions are convoluted functions, RlnK_eq = {f(1/T)* g(T)} and RTlnK_eq = {f(T)* g(lnT)}, where the primary linear functions f(1/T) and f(T) are modified and transformed into parabolic curves by the secondary functions g(T) and g(lnT), respectively. Convoluted functions are consistent with biphasic dual-structure partition function, {DS-PF} = {M-PF} ∙ {T-PF} ∙ {ζ_w}, composed by ({M-PF} (Density Entropy), {T-PF}) (Intensity Entropy), and {ζ_w} (implicit solvent). In the present paper, after recalling the essential aspects of the model, we outline the importance of considering the solvent as “implicit” in chemical and biochemical reactions. Moreover, we compare the information obtained by computer simulations using the models till now proposed with “explicit” solvent, showing the mess of information lost without considering the experimental approach of the EAM model. Full article

Optimization of the enthalpy component of binding thermodynamics of drug candidates is a successful pathway of rational molecular design. However, the large size and missing hydration structure of target-ligand complexes often hinder such optimizations with quantum mechanical (QM) methods. At the same time, QM calculations are often necessitated for proper handling of electronic effects. To overcome the above problems, and help the QM design of new drugs, a protocol is introduced for atomic level determination of hydration structure and extraction of structures of target-ligand complex interfaces. The protocol is a combination of a previously published program MobyWat, an engine for assigning explicit water positions, and Fragmenter, a new tool for optimal fragmentation of protein targets. The protocol fostered a series of fast calculations of ligand binding enthalpies at the semi-empirical QM level. Ligands of diverse chemistry ranging from small aromatic compounds up to a large peptide helix of a molecular weight of 3000 targeting a leukemia protein were selected for systematic investigations. Comparison of various combinations of implicit and explicit water models demonstrated that the presence of accurately predicted explicit water molecules in the complex interface considerably improved the agreement with experimental results. A single scaling factor was derived for conversion of QM reaction heats into binding enthalpy values. The factor links molecular structure with binding thermodynamics via QM calculations. The new protocol and scaling factor will help automated optimization of binding enthalpy in future molecular design projects. Full article

The precise description of solute-water interactions is essential to understand the chemo-physical nature in hydration processes. Such a hydration thermodynamics for various solutes has been explored by means of explicit or implicit solvation methods. Using the Poisson-Boltzmann solvation model, the implicit models are well designed to reasonably predict the hydration free energies of polar solutes. The implicit model, however, is known to have shortcomings in estimating those for non-polar aromatic compounds. To investigate a cause of error, we employed a novel systematic framework of quantum-mechanical/molecular-mechanical (QM/MM) coupling protocol in explicit solvation manner, termed DFT-CES, based on the grid-based mean-field treatment. With the aid of DFT-CES, we delved into multiple energy parts, thereby comparing DFT-CES and PB models component-by-component. By applying the modified PB model to estimate the hydration free energies of non-polar solutes, we find a possibility to improve the predictability of PB models. We expect that this study could shed light on providing an accurate route to study the hydration thermodynamics for various solute compounds. Full article