Evaluating the stability of disulfide bridges in proteins: a torsional potential energy surface for diethyl disulfide

Disulfide bonds formed by the oxidation of cysteine residues in proteins are the major form of intra- and inter-molecular covalent linkages in the polypeptide chain. To better understand the conformational energetics of this linkage, we have used the MP2(full)/6-31G(d) method to generate a full potential energy surface (PES) for the torsion of the model compound diethyl disulfide (DEDS) around its three critical dihedral angles (χ₂, χ₃, χ₂′). The use of ten degree increments for each of the parameters resulted in a continuous, fine-grained surface. This allowed us to accurately predict the relative stabilities of disulfide bonds in high resolution structures from the Protein Data Bank. The MP2(full) surface showed significant qualitative differences from the PES calculated using the Amber force field. In particular, a different ordering was seen for the relative energies of the local minima. Thus, Amber energies are not reliable for comparison of the relative stabilities of disulfide bonds. Surprisingly, the surface did not show a minimum associated with χ₂～ ? 60°, χ₃～90, χ₂′～ ? 60°. This is due to steric interference between Hα atoms. Despite this, significant populations of disulfides were found to adopt this conformation. In most cases this conformation is associated with an unusual secondary structure motif, the cross-strand disulfide. The relative instability of cross-strand disulfides is of great interest, as they have the potential to act as functional switches in redox processes.     

Hydrogen bond analysis of confined water in mesoporous silica using the reactive force field

ABSTRACT

The structural and dynamical properties of water confined in nanoporous silica with a pore diameter of 2.7?nm were investigated by performing large-scale molecular dynamics simulations using the reactive force field. The radial distribution function and diffusion coefficient of water were calculated, and the values at the centre of the pore agreed well with experimental values for real water. In addition, the pore was divided into thin coaxial layers, and the average number of hydrogen bonds, hydrogen bond lifetime and hydrogen bond strength were calculated as a function of the radial distance from the pore central axis. The analysis showed that hydrogen bonds involving silanol (Si–OH) have a longer lifetime, although the average number of hydrogen bonds per atom does not change from that at the pore centre. The longer lifetime, as well as smaller diffusion coefficient, of these hydrogen bonds is attributed to their greater strength.     

GPU-accelerated molecular dynamics simulation of solid covalent crystals

Graphics processing unit (GPU) is becoming a powerful computational tool in science and engineering. In this paper, different from previous molecular dynamics (MD) simulation with pair potentials and many-body potentials, two MD simulation algorithms implemented on a single GPU are presented to describe a special category of many-body potentials – bond order potentials used frequently in solid covalent materials, such as the Tersoff potentials for silicon crystals. The simulation results reveal that the performance of GPU implementations is apparently superior to their CPU counterpart. Furthermore, the proposed algorithms are generalised, transferable and scalable, and can be extended to the simulations with general many-body interactions such as Stillinger–Weber potential and so on.     

Molecular structure,spectroscopic (FT-IR,FT-Raman,UV–vis), NBO,thermochemistry analysis of bis(thiourea)zinc(II) chloride crystals

The experimental and theoretical studies on the molecular structure and vibrational spectra of bis(thiourea)zinc(II) chloride (BTZC) crystals were investigated. The Fourier transform infrared, Fourier transform Raman and UV–vis spectra of BTZC were recorded. The molecular geometry and vibrational frequencies of BTZC in the ground state were calculated by using B3LYP with LANL2DZ as basis set. Comparison of the observed structural parameters of BTZC with single-crystal X-ray studies yields a good agreement. Vibrational analysis of the simultaneous IR and Raman activation of the Zn–Cl stretching mode in the molecule provides the evidence for the charge transfer interaction taking place within the molecule. The energy and oscillator strength are calculated by time-dependent density functional theory. The simulated spectra satisfactorily coincide with the experimental spectra.     

The Spherical Expansion of H2 Dimer Interaction Energy by Double Symmetry-Adapted Perturbation Theory

Abstract

The weak interaction energy of H₂ dimer is studied by double symmetry-adapted perturbation theory (SAPT) within second-order of intermolecular and intramonomer perturbation for molecular simulations. The assumed orientations of H₂ dimer are linear, parallel, T type and X type. Among four orientations T orientation is the most stable, while linear orientation is the most repulsive. The second-order dispersion energy E _disp ⁽²⁾ is the most attractive contribution in all orientations. The interaction energy has the anisotropy, so we expressed our total interaction energy by the spherical expansion to compare with the experimental value. The isotropic interaction energy is about 85% of the experimental value.     

Quantum chemical study of the structure and properties of citrinin

Detailed structures and electronic properties of three tautomeric forms of the toxin citrinin were investigated using several quantum calculation methods. Energetic preference of the predominant p- and o-quinone methide tautomeric forms is dependent on the method of calculation. A previously unstudied carboxylic acid enol tautomer was calculated to be surprisingly stable in vacuo, being within 2.5 kcal mol^? 1 at the B3LYP/6-311++G(2d,2p) level of theory. Despite differences in bond nature and connectivity of tautomers, the natural bond orbital analysis revealed that tautomeric forms share similar natural charges and natural electron configurations. Calculated bond lengths corresponded with experimentally observed values and assignments for the calculated infrared vibrational frequencies are reported.     

Looking After Chronically III Dogs: Impacts on the Caregiver's Life

ABSTRACT

Studies in human medicine show that care of chronically ill family members can affect the caregiver's life in several ways and cause “caregiver burden.” Companion animals are offered increasingly advanced veterinary treatments, sometimes involving home care. Owners choosing such treatments could thus face similar challenges when caring for their animals. This qualitative study uncovers impacts on an owner's life, when attending to the care of an aged or chronically ill dog and reflects on the differing roles of caregivers with animal and human patients. Twelve dog owners were selected for in-depth interviews based on the dogs' diagnoses, and the choice of treatments and care expected to affect the owner's life. Interviews were recorded, transcribed, and analyzed qualitatively. The dog owners reported several changes in their lives due to their dog's condition: practicalities like extra care, changes in use of the home, and restrictions relating to work, social life, and finances. These were time-consuming, tough, and annoying, but could often be dealt with through planning and prioritizing. Changes in the human–dog relationship and activities caused sadness and frustration, which in turn led to feelings of guilt, and in some cases created a feeling of loss. Also, concerns about the progress of the dog's condition, it's welfare, and euthanasia brought emotional distress and many doubts. The owners did, however, respond to the changes differently and as a result experienced different effects on their own life. This study confirms that the situations of caregivers with human and animal patients are in some ways similar, yet the study also identifies and reflects on some of the differences. These include the caregiver role and the options of assistance as well as euthanasia. Veterinary staff are urged to inform owners about possible impacts on their lives when considering careconsuming treatments, and to be aware of the need for support during treatment as well as in decisions about euthanasia.     

Development of a Model For Estimating the Size and Dynamics of the Pet Dog Population

Abstract

A conceptual model was developed to describe the dynamics of the pet dog population. The model synthesizes existing data collected for a variety of purposes to estimate the size of the various components of the pet dog population in Washington and Iowa during 1991. The total population mortality rate was estimated as 12.4% per year. Animal shelters in Washington and Iowa handled 7.6% and euthanized 4.0% of the dog population in those two states. When these estimates were extrapolated to the entire U.S. dog population, the model predicted that the total annual turnover in owned dogs was 14.7%, or 7.71 million dogs, that 4 million dogs were handled by animal shelters, and that 2.1 million were euthanized. It was also estimated that 79% of all female dogs were spayed, that household breeding could be attributed to less than one-fifth (18.7%) of the female dogs in the reproductive pool, and that the number of owners contributing to total dog population turnover through failure to retain their dog (103,453) was approximately three times the number of owners who allowed their female dogs to be bred (32,513).     

Influence of HOCl…O3 and HOCl…HOCl interactions on the stability of O3(HOCl)2 complexes: a theoretical study

We have analysed the role of HOCl…O₃ and HOCl…HOCl interactions on the stability of four estimated O₃(HOCl)₂ complexes by means of ab initio molecular orbital calculations. It is predicted that the O₃(HOCl) + HOCl reaction is more energetically favourable than (HOCl)₂ + O₃ one. In all complexes, HOCl…HOCl interaction is stronger than HOCl…O₃ one. The results show that the HOCl…O₃ interaction strengthens the HOCl…HOCl one. On the other hand, O…H interaction in HOCl…O₃ moiety is strengthened when it interacts with HOCl. Quantum theory of atoms in molecules predicts that the weak interactions in O₃(HOCl)₂ complexes have electrostatic characteristic. In all complexes, the charge transfer from O₃ to (HOCl)₂ is expected from natural bond orbital analysis.     

The Stabilizing Effects of O-glycosylation on the Secondary Structural Integrity of the Designed α-loop-α motif by Molecular Dynamics Simulations

Abstract

In this study, various 400 ps molecular dynamics simulations were conducted to determine the stabilizing effect of O-glycosylation on the secondary structural integrity of the design α-loop-α motif, which has the optimal loop length of 7 Gly residues (denoted as N-A₁₆G₇A₁₆-C). In general, O-glycosylation stabilizes the structural integrity of the model peptide regardless of the length and position of glycosylation sites because it decreases the opportunity for water molecules to compete for the intramolecular hydrogen bonds. The designed peptide exhibits the highest helicity when residues 11 and 31 are replaced with Ser residues followed by O-linked with 3 galactose residues, representing the “face-to-face” glycosylation near the loop. In this case, the loop exhibits an extended conformation and several new hydrogen bonds are observed between the main chain of the loop and the galactose residues, resulting in decreasing the fluctuation and increasing the stability of the entire peptide. When the glycosylation are made close to the loop, the secondary structural integrity of the α-loop-α motif increases with the number of galactose residues. In addition, “face- to-face” glycosylation increases the structural integrity of this motif to a greater extent than “back-to-back” glycosylation. However, when the glycosylation are created away from the loop and near the N- and C-termini, no general rule is found for the stabilizing effect.