Processing and Technology of Dairy Products: A Special Issue

peer-reviewedThis is the Editorial for a Special Issue " Processing and Technology of Dairy Products

Molecular modeling of zinc paddlewheel molecular complexes and the pores of a flexible metal organic framework

A new all-atom first-principles force field (FF) is constructed for the bimetallic, four-bladed zinc paddlewheel (ZPW) motif. Zinc-ligand interactions are described via Morse functions and the angular geometry at the metal centers is modeled with a pure ligand-ligand repulsion term. The ZPW-FF is principally based on 15 DFT-optimized model systems of general formula ZnPR.nL, where ZnP is the base Zn2(O2CR)4 unit, R = H, CH3 or CF3, L = NH3 or pyridine, and n = 0, 1 or 2. It correctly generates the distorted tetrahedral coordination of the uncapped [Zn2(O2CR)4] species in their ground states as well as giving reasonable structures and energies for the higher symmetry D4h transition state conformations. The zinc-ligand Morse function reference distance, r 0 , is further refined against 30 complexes located in the Cambridge Structural Database and this FF is applied to pore models of the flexible metal-organic framework (MOF) [Zn(bdc)2(dabco)]n (bdc = 1,4-benzendicarboxylate; dabco = 1,4-diazabicyclo(2.2.2)octane). A single pore model reproduces the unit cell of the evacuated MOF system while a 3×3 grid model is necessary to provide good agreement with the observed pronounced structural changes upon adsorption of either dimethylformamide or benzene

Density functional calculations reveal a flexible version of the copper paddlewheel unit : implications for metal organic frameworks

Density functional theory calculations on [Cu2(O2CR)4L2] systems reveal a change in ground state with increasing Cu-L bond strength. For L = N-heterocyclic carbene (NHC), the Jahn-Teller axis switches from parallel to orthogonal to the Cu-Cu vector and the copper coordination geometry becomes highly flexible. While the calculated dimer/monomer equilibrium for isolated complexes slightly favours monomers, the preformed paddlewheel units embedded in many metal organic frameworks are potential targets for developing novel materials

Metal binding to amyloid-β1–42: a ligand field molecular dynamics study

Ligand field molecular mechanics simulation has been used to model the interactions of copper(II) and platinum(II) with the amyloid-β1–42 peptide monomer. Molecular dynamics over several microseconds for both metalated systems are compared to analogous results for the free peptide. Significant differences in structural parameters are observed, both between Cu and Pt bound systems as well as between free and metal-bound peptide. Both metals stabilize the formation of helices in the peptide as well as reducing the content of β secondary structural elements compared to the unbound monomer. This is in agreement with experimental reports of metals reducing β-sheet structures, leading to formation of amorphous aggregates over amyloid fibrils. The shape and size of the peptide structures also undergo noteworthy change, with the free peptide exhibiting globular-like structure, platinum(II) system adopting extended structures, and copper(II) system resulting in a mixture of conformations similar to both of these. Salt bridge networks exhibit major differences: the Asp23-Lys28 salt bridge, known to be important in fibril formation, has a differing distance profile within all three systems studied. Salt bridges in the metal binding region of the peptide are strongly altered; in particular, the Arg5-Asp7 salt bridge, which has an occurrence of 71% in the free peptide, is reduced to zero in the presence of both metals

Benchmarking of copper(II) LFMM parameters for studying amyloid-β peptides

Ligand field molecular mechanics (LFMM) parameters have been benchmarked for copper (II) bound to the amyloid-β1–16 peptide fragment. Several density functional theory (DFT) optimised small test models, representative of different possible copper coordination modes, have been used to test the accuracy of the LFMM copper bond lengths and angles, resulting in errors typically less than 0.1 Å and 5°. Ligand field molecular dynamics (LFMD) simulations have been carried out on the copper bound amyloid-β1–16 peptide and snapshots extracted from the subsequent trajectory. Snapshots have been optimised using DFT and the semi-empirical PM7 method resulting in good agreement against the LFMM calculated geometry. Analysis of substructures within snapshots shows that the larger contribution of geometrical difference, as measured by RMSD, lies within the peptide backbone, arising from differences in DFT and AMBER, and the copper coordination sphere is reproduced well by LFMM. PM7 performs excellently against LFMM with an average RMSD of 0.2 Å over 21 tested snapshots. Further analysis of the LFMD trajectory shows that copper bond lengths and angles have only small deviations from average values, with the exception of a carbonyl moiety from the N-terminus, which can act as a weakly bound fifth ligand

Ligand field molecular dynamics simulation of Pt(II)-phenanthroline binding to N-terminal fragment of amyloid-β peptide

We report microsecond timescale molecular dynamics simulation of the complex formed between Pt(II)-phenanthroline and the 16 N-terminal residues of the Aβ peptide that is implicated in the onset of Alzheimer’s disease, along with equivalent simulations of the metal-free peptide. Simulations from a variety of starting points reach equilibrium within 100 ns, as judged by root mean square deviation and radius of gyration. Platinum-bound peptides deviate rather more from starting points, and adopt structures with larger radius of gyration, than their metal-free counterparts. Residues bound directly to Pt show smaller fluctuation, but others actually move more in the Pt-bound peptide. Hydrogen bonding within the peptide is disrupted by binding of Pt, whereas the presence of salt-bridges are enhanced

Effect of addition of gelatin on the rheological and microstructural properties of acid milk protein gels

To gain an understanding of the gelation mechanism of mixtures of milk proteins and gelatin, rheological and microstructural properties of the mixtures were characterized following four stages. During the acidification stage (at 45\ua0°C), the presence of gelatin at sufficient concentration (higher than 1%) led to a lower storage modulus (G′) than that of the pure milk protein gels and a more heterogenous microstructure with larger milk protein clusters was formed. During the cooling (from 45 to 10\ua0°C) and annealing stage s (at 10\ua0°C), the G′ of the gels increased because of both milk gel enhancement and gelatin gelation. Higher concentrations of gelatin led to earlier formation of strand-like structures, seen in the micrographs. The gelation of gelatin changed the microstructure of whey protein isolate (WPI) gel dramatically, while gels of milk protein concentrate (MPC) and skim milk powder (SMP) maintained the typical milk gel network and gelatin formed strands and films without destroying the existing gels. During the heating stage (from 10 to 45\ua0°C), gelatin strands were melted and the G′ of the mixed gels tended to revert to the value at the end of the acidification stage, indicating that the changes caused by gelatin in the microstructure of milk protein gels after acidification are reversible. Additionally, gelatin enhanced the water holding capacity (WHC) of the gels (no serum expulsion was observed for gels containing ≥1% gelatin), without increasing gel firmness significantly

A Framework for Incorporating Behavioural Change into Individual-Level Spatial Epidemic Models

During epidemics, people will often modify their behaviour patterns over time in response to changes in their perceived risk of spreading or contracting the disease. This can substantially impact the trajectory of the epidemic. However, most infectious disease models assume stable population behaviour due to the challenges of modelling these changes. We present a flexible new class of models, called behavioural change individual-level models (BC-ILMs), that incorporate both individual-level covariate information and a data-driven behavioural change effect. Focusing on spatial BC-ILMs, we consider four "alarm" functions to model the effect of behavioural change as a function of infection prevalence over time. We show how these models can be estimated in a simulation setting. We investigate the impact of misspecifying the alarm function when fitting a BC-ILM, and find that if behavioural change is present in a population, using an incorrect alarm function will still result in an improvement in posterior predictive performance over a model that assumes stable population behaviour. We also find that using spike and slab priors on alarm function parameters is a simple and effective method to determine whether a behavioural change effect is present in a population. Finally, we show results from fitting spatial BC-ILMs to data from the 2001 U.K. foot and mouth disease epidemic

Computational study of the structure and electronic circular dichroism spectroscopy of blue copper proteins

The calculation of the electronic circular dichroism (CD) spectra of the oxidised form of the blue copper proteins plastocyanin and cucumber basic protein and the relationship between the observed spectral features and the structure of the active site of the protein is investigated. Excitation energies and transition strengths are computed using multi reference configuration interaction, and it is shown that computed spectra based on coordinates from the crystal structure or a single structure optimised in quantum mechanics/molecular mechanics (QM/MM) or ligand field molecular mechanics (LFMM) are qualitatively incorrect. In particular, the rotational strength of the ligand to metal charge transfer band is predicted to be too small or have the incorrect sign. By considering calculations on active site models with modified structures it is shown that the intensity of this band is sensitive to the non-planarity of the histidine and cysteine ligands coordinated to copper. Calculation of the ultraviolet absorption and CD spectra based upon averaging over many structures drawn from a LFMM molecular dynamics simulation are in good agreement with experiment, and superior to analogous calculations based upon structures from a classical molecular dynamics simulation. This provides evidence that the LFMM force field provides an accurate description of the molecular dynamics of these proteins