A practical approach that enables one to calculate the standard free energy of binding from a one-dimensional potential mean force (PMF) is proposed. Umbrella sampling and weighted histogram analysis method are used generate PMF along reaction coordinate binding. At each point, restraint applied orthogonal make possible determination volume sampled by ligand. The an arbitrary unbound restrained bound form calculated ratio integrated over region unbound. Adding changes standard-state...

The use of bare cluster models to understand the nature zeolite–substrate interactions may be improved take account environment Brønsted acid site. We consider two for introducing electrostatic effects zeolite lattice. first involves generating a specialised correction potential by fitting non-periodic array ca. 60 point charges difference between and periodic potentials. second starts atomic infinite lattice then builds up classical 2000 atoms into which QM is embedded. Such embedded...

Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, infection control. However, our understanding of this crucial process still rather limited because experimental conceptual challenges. Here, we used proteomics, microbial genetics, competitive infections, computational approaches obtain a comprehensive overview Salmonella nutrition mouse typhoid fever model. The data revealed that accessed an unexpectedly diverse set...

The aim of this study was to investigate the effect manuka honey, artificial honey and an antibacterial component (methylglyoxal) on cell division in methicillin-resistant Staphylococcus aureus (MRSA). Viability epidemic MRSA-15 NCTC 13142 incubated with methylglyoxal determined, structural effects monitored by electron microscopy. Activity murein hydrolase (a peptidoglycan-degrading enzyme implicated separation, encoded atl) estimated wall hydrolysis zymography; expression atl quantified...

A hybrid quantum mechanical/molecular mechanical approach is used to elucidate structural and energetic features of amide hydrolysis by the enzyme papain. The role in stabilizing thiolate−imidazolium ion pair examined potential energy pathway for subsequent attack cysteine anion proton transfer from imidazolium cation determined. reaction found be concerted rather than stepwise, transition state located. effect residue mutations both on stability barrier explored agreement with experiment....

Invasive Salmonella infection is an important health problem that worsening because of rising antimicrobial resistance and changing serovar spectrum. Novel vaccines with broad coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved in a mouse typhoid fever model, identified antigen candidates conferred partial protection against lethal disease. Antigen properties such as high vivo abundance or immunodominance convalescent individuals...

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen. Its resistance to multiple antibiotics and its prevalence in healthcare establishments make it a serious threat human health that requires novel interventions. Manuka honey broad-spectrum antimicrobial agent gaining acceptance the topical treatment of wounds. Because mode action only partially understood, proteomic genomic analysis was used investigate effects manuka on MRSA at molecular level. Two-dimensional gel...

We describe the use of density functional theory (DFT-D) and semiempirical (AM1-D PM3-D) methods having an added empirical dispersion correction, to treat noncovalent interactions between molecules involving sulfur atoms. The DFT-D method, with BLYP B3LYP functionals, was judged against a small-molecule database sulfur-π, S-H···S, C-H···S for which high-level MP2 or CCSD(T) estimates structures binding interaction energies are available. This also used develop appropriate AM1-D PM3-D...

An exciting new family of hydrophilic ligands for the selective extraction Am(<sc>iii</sc>) from spent nuclear fuel are reported herein.

The first examples of 4,7-disubstituted 2,9-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzo-triazin-3-yl)-1,10-phenanthroline (CyMe4-BTPhen) ligands are reported herein. Evaluating the kinetics, selectivity and stoichiometry actinide(iii) lanthanide(iii) radiotracer extractions has provided a mechanistic insight into extraction process. For time, it been demonstrated that metal ion kinetics can be modulated by backbone functionalisation promising new CHON compliant candidate ligand...

Understanding the fundamental reactivity of polymetallic complexes is challenging due to complexity their structures with many possible bond breaking and forming processes. Here, we apply ion mobility mass spectrometry coupled density functional theory investigate disassembly mechanisms energetics a family heterometallic rings rotaxanes general formula [NH

Following electrospray ionization, it is common for analytes to enter the gas phase accompanied by a charge-carrying ion, and in most cases, this addition required enable detection mass spectrometer. These small charge carriers may not be influential solution but can markedly tune analyte properties phase. Therefore, measuring their relative influence on target molecule assist our understanding of structure stability analyte. As formed adducts are usually distinguishable mass, differences...

A new hybrid quantum mechanical/molecular mechanical model of solvation is developed and used to describe the structure dynamics small fluoride/water clusters, using an ab initio wave function ion a fluctuating charge potential waters. Appropriate parameters for water–water fluoride–water interactions are derived, with fluoride anion being described by density functional theory large Gaussian basis. The role solvent polarization in determining energetics F(H2O)4− clusters investigated,...

The location of stationary points on potential energy surfaces calculated by hybrid quantum mechanical (QM)/molecular (MM) methods, allowing for relaxation both the QM and MM regions, is discussed illustrated with results from a study enzyme chorismate mutase. Enhanced interactions between carboxylate groups neighboring arginine residues are shown to be important in catalysis prephenate this enzyme. treatment interface regions studied calculations series models amino acids. © 2000 John Wiley...

A simple procedure utilizing the molecular orbital (MO) Hessian, second derivative of Hartree–Fock (HF) energy with respect to MO coefficient perturbations, has been proposed in interpretation anomalous analytic HF derivatives. The nature self-consistent field (SCF) harmonic vibrational frequencies and infrared (ir) intensities 2B2 2A2 excited states NO2 HCO2 have studied detail. By suitable partitioning expression, an association between abnormal force constants, dipole moment derivatives,...

The performance of a number computational approaches based upon density functional theory (DFT) for the accurate description carbohydrate–π interactions is described. A database containing interaction energies small representative complexes, computed at high ab initio level, described, and used to judge 18 different functionals including M05 M06 families as well DFT method augmented with empirical dispersive corrections (DFT-D). DFT-D are found perform particularly well, whilst traditional...

Abstract Understanding the (dis)assembly mechanisms of large metallosupramolecules is critical in their design, stability and application. The inherent complexity these structures leads to many potential pathways for combining (or separating) constituent building blocks, which makes this task difficult. Here we use collision-induced dissociation mass spectrometry study disassembly heterometallic complexes. Collisional activation formation a series previously unknown smaller ring products...

An embedded cluster model, employing a point charge field to correctly account for the electrostatic effect of surrounding lattice, is used study adsorption water and methanol at zeolite Bro/nsted acid sites. The effects both electron correlation (studied second order Mo/ller–Plesset (MP2) density functional theory (DFT) levels) are reflected in predicted substrate structures, binding energies 1H NMR shifts. Both result enhanced yield good agreement with experiment, an increased degree...

Many metallabenzene complexes appear to exhibit an enhanced thermodynamic stability which has been attributed the concept of aromaticity. Analysis ring currents induced by a magnetic field, either direct visualization or considering nuclear nucleus-independent chemical shielding values (NMR NICS), have become useful theoretical tools characterize aromaticity many molecules involving main group elements. We analyzed 21 metallabenzenes using variations these techniques, take account large core...

Syringomycin halogenase (SyrB2) is a non-heme Fe(II)/alpha-ketoglutarate (alphaKG)-dependent enzyme which catalyses halogenation of saturated hydrocarbons, but unlike other closely related enzymes, does not catalyse the corresponding hydroxylation reaction. We have carried out density functional theory (DFT) calculations to try understand this specificity. Calculations include only basic six coordinate iron centre suggest that both and are feasible by rebound mechanism. reaction inhibited...

Carbohydrate–protein recognition has been studied by electronic structure calculations of complexes fucose and glucose with toluene, p-hydroxytoluene 3-methylindole, the latter aromatic molecules being analogues phenylalanine, tyrosine tryptophan, respectively. We use mainly a density functional theory model empirical corrections for dispersion interactions (DFT-D), this method validated comparison limited number high level ab initio calculations. have calculated both binding energies as...