Experimental magnetic form factors in Co3V2O8: A combined study of ab initio calculations, magnetic Compton scattering and polarized neutron diffraction

We present a combination of ab initio calculations, magnetic Compton scattering and polarized neutron experiments, which elucidate the density distribution of unpaired electrons in the kagome staircase system Co3V2O8. Ab initio wave functions were used to calculate the spin densities in real and momentum space, which show good agreement with the respective experiments. It has been found that the spin polarized orbitals are equally distributed between the t2g and the eg levels for the spine (s) Co ions, while the eg orbitals of the cross-tie (c) Co ions only represent 30% of the atomic spin density. Furthermore, the results reveal that the magnetic moments of the cross-tie Co ions, which are significantly smaller than those of the spine Co ions in the zero-field ferromagnetic structure, do not saturate by applying an external magnetic field of 2 T along the easy axis a, but that the increasing bulk magnetization originates from induced magnetic moments on the O and V sites. The refined individual magnetic moments are mu(Co_c)=1.54(4) mu_B, mu(Co_s)=2.87(3) mu_B, mu(V)=0.41(4) mu_B, mu(O1)=0.05(5) mu_B, mu(O2)=0.35(5) mu_B, and; mu(O3)=0.36(5) mu_B combining to the same macroscopic magnetization value, which was previously only attributed to the Co ions

Mechanism of proteolysis in matrix metalloproteinase-2 revealed by QM/MM modeling

The mechanism of enzymatic peptide hydrolysis in matrix metalloproteinase-2 (MMP-2) was studied at atomic resolution through quantum mechanics/molecular mechanics (QM/MM) simulations. An all-atom three-dimensional molecular model was constructed on the basis of a crystal structure from the Protein Data Bank (ID: 1QIB), and the oligopeptide Ace-Gln-Gly∼Ile-Ala-Gly-Nme was considered as the substrate. Two QM/MM software packages and several computational protocols were employed to calculate QM/MM energy profiles for a four-step mechanism involving an initial nucleophilic attack followed by hydrogen bond rearrangement, proton transfer, and C—N bond cleavage. These QM/MM calculations consistently yield rather low overall barriers for the chemical steps, in the range of 5–10 kcal/mol, for diverse QM treatments (PBE0, B3LYP, and BB1K density functionals as well as local coupled cluster treatments) and two MM force fields (CHARMM and AMBER). It, thus, seems likely that product release is the rate-limiting step in MMP-2 catalysis. This is supported by an exploration of various release channels through QM/MM reaction path calculations and steered molecular dynamics simulations

Fluorescent properties of the kindling fluorescent protein (KFP) at acidic pH values

Kindling fluorescent protein (KFP) is the photoswitchable protein which can be used in high-resolution microscopy and as a quencher in FRET-sensors. Fluorescent properties of KFP depend on pH value. In this paper we investigate the influence of pH on the spectral properties and kindling/quenching ability of KFP in the acidic pH region.Shift to the acidic region leads to the increase of fluorescence intensity of KFP over time. The excitation spectrum has a new peak near 455nm, giving two peaks - 530 and 590nm – in emission spectrum. We can assume that this maximum corresponds to the appearance of protonated form of the KFP chromophore.Analysis of fluorescence decay curves of KFP in H2O and D2O showed the presence of the kinetic isotope effect, which can be caused by the proton transfer from solvent molecules to the KFP chromophore, confirming the hypothesis that in the acidic pH region protonated form of KFP chromophore appears.At acidic pH irradiation of KFP with green light doesn’t lead to fluorescence increase, while blue light doesn’t quench the fluorescence. It means that KFP is also in the bright form, and there is no conformational states of protein which can be quenched by blue light

Understanding the non-catalytic behavior of human butyrylcholinesterase silent variants: Comparison of wild-type enzyme, catalytically active Ala328Cys mutant, and silent Ala328Asp variant

© 2016 Elsevier Ireland LtdConformational dynamics of wild-type human butyrylcholinesterase (BChE), two mutants of residue Ala328, the catalytically active Ala328Cys, and the catalytically inactive (silent) Ala328Asp, and their interactions with butyrylcholine were studied. The aim was to understand the molecular mechanisms by which point mutations may lead to silent BChE variant or alter catalytic activity. Importance of BChE natural variants is due to medical consequences, i.e. prolonged apnea, following administration of the myorelaxant esters, succinylcholine and mivacurium. Comparison of molecular dynamics (MD) simulations for the three model systems showed that: 1) the active mutant Ala328Cys mutant has some changes in configuration of catalytic residues, which do not prevent binding of butyrylcholine to the active site; 2) in the naturally-occurring silent variant Ala328Asp, the Asp328 carboxylate may either form a salt bridge with Lys339 or a H-bond with His438. In the first case, the Ω-loop swings off the gorge, disrupting the π-cation binding site and the catalytic triad. In the second case, binding of cationic substrates in the catalytic center is also impaired. MD simulations carried out in 0.15 M NaCl, close to physiological ionic strength conditions, favored the second situation. It was seen that Asp328 forms a H-bond with the catalytic triad His438, which in turn disrupts the catalytic machinery. Therefore, we concluded that the Ala328Asp variant is not catalytically active because of that dramatic event. Computational results, consistent with in vitro biochemical data and clinical observations, validate our MD approach

An overview of progress in electrolytes for secondary zinc-air batteries and other storage systems based on zinc

The revived interest and research on the development of novel energy storage systems with exceptional inherent safety, environmentally benign and low cost for integration in large scale electricity grid and electric vehicles is now driven by the global energy policies. Within various technical challenges yet to be resolved and despite extensive studies, the low cycle life of the zinc anode is still hindering the implementation of rechargeable zinc batteries at industrial scale. This review presents an extensive overview of electrolytes for rechargeable zinc batteries in relation to the anode issues which are closely affected by the electrolyte nature. Widely studied aqueous electrolytes, from alkaline to acidic pH, as well as non-aqueous systems including polymeric and room temperature ionic liquids are reported. References from early rechargeable Zn-air research to recent results on novel Zn hybrid systems have been analyzed. The ambition is to identify the challenges of the electrolyte system and to compile the proposed improvements and solutions. Ultimately, all the technologies based on zinc, including the more recently proposed novel zinc hybrid batteries combining the strong points of lithium-ion, redox-flow and metal-air systems, can benefit from this compilation in order to improve secondary zinc based batteries performance.Basque Country University (ZABALDUZ2012 program), and the Basque Country Government (Project: CIC energiGUNÉ16 of the ELKARTEK program) and the European Commission through the project ZAS: “Zinc Air Secondary innovative nanotech based batteries for efficient energy storage” (Grant Agreement 646186

Understanding the non-catalytic behavior of human butyrylcholinesterase silent variants: Comparison of wild-type enzyme, catalytically active Ala328Cys mutant, and silent Ala328Asp variant

© 2016 Elsevier Ireland Ltd.Conformational dynamics of wild-type human butyrylcholinesterase (BChE), two mutants of residue Ala328, the catalytically active Ala328Cys, and the catalytically inactive (silent) Ala328Asp, and their interactions with butyrylcholine were studied. The aim was to understand the molecular mechanisms by which point mutations may lead to silent BChE variant or alter catalytic activity. Importance of BChE natural variants is due to medical consequences, i.e. prolonged apnea, following administration of the myorelaxant esters, succinylcholine and mivacurium.Comparison of molecular dynamics (MD) simulations for the three model systems showed that: 1) the active mutant Ala328Cys mutant has some changes in configuration of catalytic residues, which do not prevent binding of butyrylcholine to the active site; 2) in the naturally-occurring silent variant Ala328Asp, the Asp328 carboxylate may either form a salt bridge with Lys339 or a H-bond with His438. In the first case, the Ω-loop swings off the gorge, disrupting the π-cation binding site and the catalytic triad. In the second case, binding of cationic substrates in the catalytic center is also impaired. MD simulations carried out in 0.15 M NaCl, close to physiological ionic strength conditions, favored the second situation. It was seen that Asp328 forms a H-bond with the catalytic triad His438, which in turn disrupts the catalytic machinery. Therefore, we concluded that the Ala328Asp variant is not catalytically active because of that dramatic event. Computational results, consistent with in vitro biochemical data and clinical observations, validate our MD approach

Molecular polymorphism of human enzymes as the basis of individual sensitivity to drugs. Supercomputer-assisted modeling as a tool for analysis of structural changes and enzymatic activity of proteins

© 2016, Springer Science+Business Media New York.The nature of individual sensitivity to drugs associated with molecular polymorphism of human enzymes is discussed. The influence of molecular polymorphism on the activity of key human esterases, in particular, cholinesterases and carboxylesterase, responsible for hydrolytic metabolism of ester-containing drugs, is analyzed. A method was developed, which involves supercomputer-assisted modeling as a tool for assessment of molecular mechanism of the impact of point mutations on the catalytic activity of enzymes. This work is a part of a study aimed at elaboration of the concept and methods of personalized medicine