Interactive molecular dynamics in virtual reality for modelling materials and catalysts.

Interactive molecular dynamics simulation in virtual reality (iMD-VR) is emerging as a promising technique in molecular science. Here, we demonstrate its use in a range of fifteen applications in materials science and heterogeneous catalysis. In this work, the iMD-VR package Narupa is used with the MD package, DL_POLY [1]. We show how iMD-VR can be used to: (i) investigate the mechanism of lithium fast ion conduction by directing the formation of defects showing that vacancy transport is favoured over interstitialcy mechanisms, and (ii) guide a molecule through a zeolite pore to explore diffusion within zeolites, examining in detail the motion of methyl n-hexanoate in H-ZSM-5 zeolite and identifying bottlenecks restricting diffusion. iMD-VR allows users to manipulate these systems intuitively, to drive changes in them and observe the resulting changes in structure and dynamics. We make these simulations available, as a resource for both teaching and research. All simulation files, with videos, can be found online (https://doi.org/10.5281/zenodo.8252314) and are provided as open-source material.

Data on the intermolecular interactions of 1,1,1,2-tetrafluoroethane liquids from molecular dynamics simulations.

Detailed atomistic interactions of 1,1,1,2-tetrafluoroethane (HFA-134a) liquid were presented in a data format, namely, DL_ANALYSER Notation for Atomic Interactions (DANAI), that annotates precisely the nature of interactions that is discoverable and searchable without having to resolve to diagrammatic illustrations. The datasets were obtained from raw atomic trajectory files of HFA-134a pure liquid models produced by using DL_POLY molecular dynamics software package. The trajectory datafiles contain expressions of atomic species in a natural chemical sense, and hence, provide localized key interactions, 'at a glance', of the liquid model on otherwise a typically disordered system consists of complex network of intermolecular interactions. The data provide insights to detailed structural behavior of molecules in liquid phase, and can be used as cheminformatics comparative investigations, linking to other molecular system models that contain similar interaction types and chemical species. This can form the foundation of investigations into the role of HFA-134a plays within different applications. For example, it can be used to compare structural and atomic interaction differences with alternative refrigerants, or as liquid propellants in pharmaceutical devices when solvating formulation ingredients.

Computational infrared and Raman spectra by hybrid QM/MM techniques: a study on molecular and catalytic material systems.

Vibrational spectroscopy is one of the most well-established and important techniques for characterizing chemical systems. To aid the interpretation of experimental infrared and Raman spectra, we report on recent theoretical developments in the ChemShell computational chemistry environment for modelling vibrational signatures. The hybrid quantum mechanical and molecular mechanical approach is employed, using density functional theory for the electronic structure calculations and classical forcefields for the environment. Computational vibrational intensities at chemical active sites are reported using electrostatic and fully polarizable embedding environments to achieve more realistic vibrational signatures for materials and molecular systems, including solvated molecules, proteins, zeolites and metal oxide surfaces, providing useful insight into the effect of the chemical environment on the signatures obtained from experiment. This work has been enabled by the efficient task-farming parallelism implemented in ChemShell for high-performance computing platforms.  This article is part of a discussion meeting issue 'Supercomputing simulations of advanced materials'.

Multiscale QM/MM modelling of catalytic systems with ChemShell.

Hybrid quantum mechanical/molecular mechanical (QM/MM) methods are a powerful computational tool for the investigation of all forms of catalysis, as they allow for an accurate description of reactions occurring at catalytic sites in the context of a complicated electrostatic environment. The scriptable computational chemistry environment ChemShell is a leading software package for QM/MM calculations, providing a flexible, high performance framework for modelling both biomolecular and materials catalysis. We present an overview of recent applications of ChemShell to problems in catalysis and review new functionality introduced into the redeveloped Python-based version of ChemShell to support catalytic modelling. These include a fully guided workflow for biomolecular QM/MM modelling, starting from an experimental structure, a periodic QM/MM embedding scheme to support modelling of metallic materials, and a comprehensive set of tutorials for biomolecular and materials modelling.

Cellulose Iß microfibril interaction with pristine graphene in water: Effects of amphiphilicity by molecular simulation.

Graphene-cellulose interactions have considerable potential in the development of new materials. In previous computational work (Biomacromolecules2016, 16, 1771), we predicted that the model 100 hydrophobic surface of cellulose interacted favourably with pristine graphene in aqueous solution molecular dynamics simulations; conversely, a model of the hydrophilic 010 surface of cellulose exhibited progressive rearrangement to present a more hydrophobic face with the graphene, with weakened hydrogen bonds between cellulose chains and partial permeation of water. Here, we extend this work by simulating the interaction in aqueous solution of the amphiphilic 110 surface of a cellulose Iß microfibril model, comprising 36 chains of 40 glucosyl residues, with an infinite sheet of pristine graphene. This face of the microfibril is of intermediate hydrophilicity and progressively associates with graphene over replicate simulations. As cellulose chains adhere to the graphene surface, forming interactions via its CH and OH groups, we observe a degree of local and global untwisting of the microfibril. Complementary rippling of the graphene surface is also observed, as it adapts to interaction with the microfibril. This adsorption process is accompanied by increased exclusion of water between cellulose and graphene although some water localises between chains at the immediate interface. The predicted propensity of a cellulose microfibril to adsorb spontaneously on the graphene surface, with mutual structural accommodation, highlights the amphiphilic nature of cellulose and the types of interactions that can be harnessed to design new graphene-carbohydrate biopolymer materials.

Laparoscopic and robot-assisted suture versus mesh hysteropexy: a retrospective comparison.

INTRODUCTION AND HYPOTHESIS: Our study was aimed at comparing the outcomes of laparoscopic and robot-assisted laparoscopic suture-based hysteropexy (SutureH) versus sacral hysteropexy using mesh (MeshH) for bothersome uterine prolapse. Our hypothesis is that MeshH is more successful and provides better uterine support than SutureH. METHODS: A retrospective cohort study of 228 consecutive women who underwent re-suspension of the uterus using uterosacral ligaments (SutureH n=97) or a "U-shaped" mesh from the sacral promontory (MeshH, n=132). Surgery was performed by laparoscopy or robot-assisted laparoscopy. Subjects were assessed at baseline, 1 year, and beyond 1 year. The null hypothesis, that SutureH and MeshH have similar success, was based on a composite outcome ("composite success"), and that they provide the same level of uterine support, was based on POP-Q point C at 1 year. "Composite success" was defined as: POP-Q point C above the hymen; absence of a vaginal bulge; no repeat uterine prolapse surgery or pessary placement. Other outcomes included improvement in symptomology using Patient Global Impression of Improvement, POP-Q point C change and complications. RESULTS: Follow-up data were available for 191 out of 228 women. "Composite success" was not significantly different between MeshH and SutureH groups (81.7% vs 84.5%, p=0.616). MeshH provided better elevation of the uterus than SutureH (point C change: -7.38cm vs -6.99cm; p<0.001). Similar symptom improvement and low complications occurred in both groups. CONCLUSIONS: Laparoscopic and robot-assisted laparoscopic suture hysteropexy and mesh sacral hysteropexy provide women with minimally invasive, durable surgical options for uterine preservation. "Composite success" was similar in the two groups, but MeshH provided better uterine support than SutureH. However, SutureH gives women an effective mesh-free option.

Combining quasielastic neutron scattering and molecular dynamics to study methane motions in ZSM-5.

Quasi-elastic neutron scattering (QENS) and molecular dynamics (MD) simulations are applied in combination to investigate the dynamics of methane in H-ZSM-5 zeolite catalysts used for methanol-to-hydrocarbons reactions. Methane is employed as an inert model for the methanol reaction feedstock, and studies are made of the fresh catalyst and used catalysts with varying levels of coke buildup to investigate the effect of coking on reactant mobility. Measurements are made in the temperature range from 5 to 373 K. Methane mobility under these conditions is found to be extremely high in fresh ZSM-5, with the majority of movements occurring too fast to be resolved by the QENS instrument used. A small fraction of molecules undergoing jump diffusion on QENS time scales is identified and found to correspond with short-range jump diffusion within single zeolite pores as identified in MD simulations. Agreement between QENS and MD mobility measurements is found to be within 50%, validating the simulation approach employed. Methane diffusion is found to be minimally affected by moderate levels of coke buildup, while highly coked samples result in the confinement of methane to single pores within the zeolite with minimal long-range diffusion.

Adulteration Detection of Edible Bird's Nests Using Rapid Spectroscopic Techniques Coupled with Multi-Class Discriminant Analysis.

Edible bird's nests (EBNs) are vulnerable to adulteration due to their huge demand for traditional medicine and high market price. Presently, there are pressing needs to explore field-deployable rapid screening techniques to detect adulteration of EBNs. The objective of this study is to explore the feasibility of using a handheld near-infrared (VIS/SW-NIR) spectroscopic device for the determination of EBN authenticity against the benchmark performance of a benchtop mid-infrared (MIR) spectrometer. Forty-nine authentic EBNs from the different states in Malaysia and 13 different adulterants (five types) were obtained and used to simulate the adulteration of EBNs at 1, 5 and 10% adulteration by mass (a total of 15 adulterated samples). The VIS/SW-NIR and MIR spectra collated were subsequently processed, modelled and classified using multi-class discriminant analysis. The VIS/SW-NIR results showed 100% correct classification for the collagen and nutrient agar classes in authenticity classification, while for the other classes, the lowest correct classification rate was 96.3%. For MIR analysis, only the karaya gum class had 100% correct classification whilst for the other four classes, the lowest rate of correct classification was at 94.4%. In conclusion, the combination of spectroscopic analysis with chemometrics can be a powerful screening tool to detect EBN adulteration.

Polyguluronate simulations shed light onto the therapeutic action of OligoG CF-5/20.

Chronic mucoid P. aeruginosa cystic fibrosis (CF) lung infections are associated with the development of a biofilm composed of anionic acetylated exopolysaccharide (EPS) alginate, electrostatically stabilised by extracellular Ca2+ ions. OligoG CF-5/20, a low molecular weight guluronate rich oligomer, is emerging as a novel therapeutic capable of disrupting mature P. aeruginosa biofilms. However, its method of therapeutic action on the mucoid biofilm EPS is not definitively known at a molecular level. This work, utilising molecular dynamics (MD) and Density-Functional Theory (DFT), has revealed that OligoG CF-5/20 interaction with the EPS is facilitated solely through bridging Ca2+ ions, which are not liberated from their native EPS binding sites upon OligoG CF-5/20 dispersal, suggesting that OligoG CF-5/20 does not cause disruptions to mature P. aeruginosa biofilms through breaking EPS-Ca2+-EPS ionic cross-links. Rather it is likely that the therapeutic activity arises from sequestering free Ca2+ ions and preventing further Ca2+ induced EPS aggregation.

Atomic-scale interactions between quorum sensing autoinducer molecules and the mucoid P. aeruginosa exopolysaccharide matrix.

Mucoid Pseudomonas aeruginosa is a prevalent cystic fibrosis (CF) lung coloniser whose chronicity is associated with the formation of cation cross-linked exopolysaccharide (EPS) matrices, which form a biofilm that acts as a diffusion barrier, sequestering cationic and neutral antimicrobials, and making it extremely resistant to pharmacological challenge. Biofilm chronicity and virulence of the colony is regulated by quorum sensing autoinducers (QSAIs), small signalling metabolites that pass between bacteria, through the biofilm matrix, regulating genetic responses on a population-wide scale. The nature of how these molecules interact with the EPS is poorly understood, despite the fact that they must pass through EPS matrix to reach neighbouring bacteria. Interactions at the atomic-scale between two QSAI molecules, C4-HSL and PQS-both utilised by mucoid P. aeruginosa in the CF lung-and the EPS, have been studied for the first time using a combined molecular dynamics (MD) and density functional theory (DFT) approach. A large-scale, calcium cross-linked, multi-chain EPS molecular model was developed and MD used to sample modes of interaction between QSAI molecules and the EPS that occur at physiological equilibrium. The thermodynamic stability of the QSAI-EPS adducts were calculated using DFT. These simulations provide a thermodynamic rationale for the apparent free movement of C4-HSL, highlight key molecular functionality responsible for EPS binding and, based on its significantly reduced mobility, suggest PQS as a viable target for quorum quenching.

The structural pathway from its solvated molecular state to the solution crystallisation of the α- and ß-polymorphic forms of para amino benzoic acid.

Para amino benzoic acid (PABA) has two well-characterised α- and ß-polymorphic forms and, whilst both crystallise in the monoclinic space group P21/n, they have quite different crystal chemistry and crystallisability behaviour. Previous work has shown that the molecular conformation deformation energy in the crystalline state is higher for the ß-form than for the α-form and that the lattice energy for the former converges more slowly than for the latter overall. This suggests that not only is there a higher barrier to crystallisation for the ß-form but also that low solution supersaturations might be needed for it to preferentially nucleate. Additionally, solute cluster propensity and solute solvation energetic analysis highlight the importance of an aqueous solvation environment in inhibiting the α-form's strong OH⋯O carboxylic acid hydrogen bond (H-bond) dimer. Despite this, the detailed molecular-scale pathway from solvated molecules to 3D crystallographic structure still remains unclear, most notably regarding how the nucleation process is activated and how, as a result, this mediates the preferential formation of either of the two polymorphic forms. Molecular dynamics (MD) simulations coupled with FTIR studies and intermolecular synthon analysis address this issue through characterisation of the propensity of the incipient bulk synthons that are important in the crystallisation of the two polymorphic forms within the solution state. MD molecular trajectory analysis within crystallisation solutions reveals a greater propensity for OH⋯O synthons (both single H-bonds and homodimers) typical of the α-form and NH⋯O synthons found in both the α- and ß-forms when compared to aqueous solution but much lower propensities for the ß-form's "fingerprinting" OH⋯N and π-π stacking synthons. In contrast, data from the aqueous solution environment reveals a much greater propensity for the ß-form's π-π interaction synthons. IR dilution studies in acetonitrile in the carbonyl region reveal the presence of two CO vibrational stretching bands, whose relative intensities vary as a function of solution dilution. These were assigned to the solvated PABA monomer and a COOH dimer of PABA. Similar data in ethanol shows a main CO stretching band with a shoulder peak suggesting a similar monomer vs. dimer speciation may exist in this solvent. The IR data is consistent with the organic solvent MD data, albeit the corresponding analysis for the aqueous solution was precluded due to the latter's strong OH vibrational mode which restricted validation in aqueous solutions.

Addressing the unfulfilled codex standard for honey for stingless bee honey through lyophilization.

Some studies have found that the nutritional values of stingless bee honey (SBH) may be similar if not more than normal honey, prompting the Malaysian government to promote it as a superfood. However, SBH does not fulfil the Codex Standard for Honey (CODEX STAN 12-19811) in terms of moisture content and the lack of protein to be analysed with Internal Standard Carbon Isotope Ratio Analysis (ISCIRA). Hence, a lyophilization process was introduced prior to stable carbon isotope analysis of SBH to address both of these issues. It was found that once moisture content was decreased to a level below 20 % for 19 SBH samples, the percentage increment of protein extracted from the samples varied between 6 and 385 % relative to protein extracted from SBH before lyophilization with nine samples found to be adulterated. Caution is necessary when lyophilizing the SBH as significant isotope shifts were seen for SCIRA and ISCIRA values. Nevertheless, the carbon isotope shifts did not change the final outcome of the 'pass' or 'fail' of the adulteration result. Overall, the removal of water from SBH is required but caution is necessary as carbon isotope shifts were observed as SBHs underwent the lyophilization process.

Detecting adulteration of stingless bee honey using untargeted 1H NMR metabolomics with chemometrics.

As stingless bee honey (SBH) is gaining in popularity in the Malaysian market, it is now prone to adulteration. The higher price of SBH compared to floral honey has led to the use of unusual adulterants such as vinegar and even floral honey to mimic the unique taste and appearance of SBH. Since the current AOAC 998.12 method fails to detect these adulterants as their δ13C values are in the range for C3 plants, untargeted 1H NMR metabolomics was proposed. Principal component analysis of SBH 1H NMR fingerprints was able to distinguish authentic SBHs from adulterated ones down to 1% adulteration level for selected adulterants. Discriminant analysis showed promising results in distinguishing the preliminary datasets of authentic SBHs from the adulterated ones, including discriminating SBHs adulterated with different adulterants derived from C3 and C4 plants. Hence, to assure any emerging adulterant can be detected, all 1H NMR regions should be considered.

Triglycine (GGG) Adopts a Polyproline II (pPII) Conformation in Its Hydrated Crystal Form: Revealing the Role of Water in Peptide Crystallization.

Polyproline II (pPII) is a left-handed 31-helix conformation, which has been observed to be the most abundant secondary structure in unfolded peptides and proteins compared to α-helix and ß-sheet. Although pPII has been reported as the most stable conformation for several unfolded short chain peptides in aqueous solution, it is rarely observed in their solid state. Here, we show for the first time a glycine homopeptide (gly-gly-gly) adopting the pPII conformation in its crystalline dihydrate structure. The single crystal X-ray structure with molecular dynamic simulation suggests that a network of water and the charged carboxylate group is critical in stabilizing the pPII conformation in solid state, offering an insight into the structures of unfolded regions of proteins and the role of water in peptide crystallization.

QM/MM Simulations of Protein Crystal Reactivity Guided by MSOX Crystallography: A Copper Nitrite Reductase Case Study.

The recently developed multiple structures from one crystal (MSOX) serial crystallography method can be used to provide multiple snapshots of the progress of enzymatic reactions taking place within a protein crystal. Such MSOX snapshots can be used as a reference for combined quantum mechanical/molecular mechanical (QM/MM) simulations of enzyme reactivity within the crystal. QM/MM calculations are used to identify details of reference states that cannot be directly observed by X-ray diffraction experiments, such as protonation and oxidation states. These reference states are then used as known fixed endpoints for the modeling of reaction paths. We investigate the mechanism of nitrite reduction in an Achromobacter cycloclastes copper nitrite reductase crystal using MSOX-guided QM/MM calculations, identifying the change in nitrite binding orientation with a change in copper oxidation state, and determining the reaction path to the final NO-bound MSOX structure. The results are compared with QM/MM simulations performed in a solvated environment.

Determinants of Newly-Diagnosed Raised Blood Pressure: The Malaysian Context.

BACKGROUND: Raised blood pressure, also known as hypertension (HPT), has been a distressing health concern among Malaysians. An upward trend is found on the prevalence of newly-diagnosed HPT, contributing to the high number of overall hypertensive patients in Malaysia. To understand the cause and reduce the economic burden caused by HPT, current research aims to examine the dependency among sociodemographic and behavioural determinants of newly-diagnosed HPT among Malaysians. METHODS: The current study uses secondary data from the Fifth National Health and Morbidity Survey (NHMS V) 2015, a population based cross-sectional study. This study uses the Bayesian Network (BN) modelling to design and build a 'causal' model and identify potential determinants and their respective conditional probability on the prevalence of newly-diagnosed HPT among Malaysians. RESULTS: This study shows that Malaysians with newly-diagnosed HPT are directly affected by the age and body mass index (BMI). Additionally, household income, sex, marital status, ethnicity, strata, education levels, occupation, fruit intake, vegetable intake, smoking status, physical activity and plain water intake indirectly affect the incidence of the newly-diagnosed HPT. CONCLUSION: These results may be helpful in implementing appropriate policies to prevent and monitor the increasing prevalence of newly-diagnosed HPT among adults in Malaysia.

Atomistic Simulation of Water Incorporation and Mobility in Bombyx mori Silk Fibroin.

Bombyx mori silk fibroin (SF) is a biopolymer that can be processed into materials with attractive properties (e.g., biocompatibility and degradability) for use in a multitude of technical and medical applications (including textiles, sutures, drug delivery devices, tissue scaffolds, etc.). Utilizing the information from experimental and computational SF studies, a simplified SF model has been produced (alanine-glycine [Ala-Gly] n crystal structure), enabling the application of both molecular dynamic and density functional theory techniques to offer a unique insight into SF-based materials. The secondary structure of the computational model has been evaluated using Ramachandran plots under different environments (e.g., different temperatures and ensembles). In addition, the mean square displacement of water incorporated into the SF model was investigated: the diffusion coefficients, activation energies, most and least favorable positions of water, and trajectory of water diffusion through the SF model are obtained. With further computational study and in combination with experimental data, the behavior/degradation of SF (and similar biomaterials) can be elucidated. Consequently, greater control of the aforementioned technologies may be achieved and positively affect their potential applications.

SARS-CoV-2 in migrant worker dormitories: Geospatial epidemiology supporting outbreak management.

BACKGROUND: Migrant worker dormitories-residential complexes where 10-24 workers share living spaces-account for the majority of cases of SARS-CoV-2 infection in Singapore. To prevent overspill of transmission to the wider population, starting in early April 2020, residents were confined to their dormitories while measures were put in place to arrest the spread of infection. This descriptive study presents epidemiological data for a population of more than 60 000 migrant workers living in two barracks-style and four apartment-style dormitories located in western Singapore from April 3 to June 10, 2020. METHODS: Our report draws from data obtained over the first 50 days of outbreak management in order to describe SARS-CoV-2 transmission in high-density housing environments. Cumulative counts of SARS-CoV-2 cases and numbers of housing units affected were analyzed to report the harmonic means of harmonic means of doubling times and their 95% confidence intervals (CI). RESULTS: Multiple transmission peaks were identified involving at least 5467 cases of SARS-CoV-2 infection across six dormitories. Our geospatial heat maps gave an early indication of outbreak severity in affected buildings. We found that the number of cases of SARS-CoV-2 infection doubled every 1.56 days (95% CI 1.29-1.96) in barracks-style buildings. The corresponding doubling time for apartment-style buildings was 2.65 days (95% CI 2.01-3.87). CONCLUSIONS: Geospatial epidemiology was useful in shaping outbreak management strategies in dormitories. Our results indicate that building design plays an integral role in transmission and should be considered in the prevention of future outbreaks.

White shrimp Litopenaeus vannamei that have received mixtures of heat-killed and formalin-inactivated Vibrio alginolyticus and V. harveyi exhibit recall memory and show increased phagocytosis and resistance to Vibrio infection.

Heat-killed Vibrio alginolyticus (HVa), formalin-inactivated V. alginolyticus (FVa), heat-killed Vibrio harveyi (HVh), formalin-inactivated V. harveyi (FVh), live V. alginolyticus (LVa), and live V. harveyi (LVh) were used in this study. White shrimp Litopenaeus vannamei receiving two mixtures (HVa + FVa) or four mixtures (HVa + FVa + HVh + FVh) served as primary exposure, and shrimp receiving LVa or LVh afterward served as secondary exposure. Shrimp receiving marine saline and then receiving either LVa or LVh served as controls. Phagocytic activity and clearance efficiency were examined in shrimp that received two mixtures after 1-8 weeks and then received LVa. Both the phagocytic activity and clearance efficiency of shrimp receiving two mixtures were significantly higher than in control shrimp after 1-8 weeks. In another experiment, phagocytic activity and clearance efficiency were examined in shrimp that received four mixtures after 1-8 weeks and then received LVa and LVh, respectively. The phagocytic activity of shrimp receiving four mixtures was significantly higher than in control shrimp after 1-8 weeks post exposure to LVa and LVh. The clearance efficiency of shrimp receiving four mixtures was significantly higher than in control shrimp after 1-6 weeks post exposure to LVa, and 1-7 weeks post exposure to LVh. In the other experiment, the survival rate of shrimp that received four mixtures after five weeks were challenged with LVa at 6.4 × 107 colony-forming units (cfu) shrimp-1 and LVh at 4.4 × 106 cfu shrimp-1. Shrimp that received marine saline for five weeks and then challenged with LVa and LVh at a same dose served as challenged controls. The survival rate of shrimp that received four mixtures was significantly higher (90%) than that of control shrimp (67%), and significantly higher (73%) than that of control shrimp (53%) after 3-7 days post challenge with LVa and LVh. It is concluded that the mixtures have feature of adjuvant and antigen, and shrimp receiving mixtures of heat-killed and formalin-inactivated V. alginolyticus and V. harveyi even after 5-8 weeks exhibit memory recall and show increased phagocytosis and resistance to Vibrio infections.