scholarly journals A Quantum Corrected Poisson-Nernst-Planck Model for Biological Ion Channels

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Jinn-Liang Liu
Keyword(s):  
Ion Channels ◽  
Classical Model ◽  
Ionic Currents ◽  
Quantum Mechanical ◽  
X Ray ◽  
X Ray Crystallography ◽  
Multi Scale ◽  
Selective Ligand ◽  
Electrophysiology Modeling ◽  
Quantum Mechanical Effects

AbstractA quantum corrected Poisson-Nernst-Planck (QCPNP) model is proposed for simulating ionic currents through biological ion channels by taking into account both classical and quantum mechanical effects. A generalized Gummel algorithm is also presented for solving the model system. Compared with the experimental results of X-ray crystallography, it is shown that the quantum PNP model is more accurate than the classical model in predicting the average number of ions in the channel pore. Moreover, the electrostatic potential has been found to reach as high as 19% difference between two models around the charged vestibule which has been shown to play a significant role in the permeation of ions through ion-selective ligand-gated or voltage-activated channels. These results indicate that the QCPNP model may be considered as a more refined continuum model that can be incorporated into a multi-scale electrophysiology modeling.

Conformational Study of 2,4-Diaryl-3-azabicyclo[3.3.1]nonan-9-ones and Their 3-Methyl Derivatives by Quantum Mechanical Calculations, NMR, and X-ray Crystallography

1994 ◽  
Vol 59 (9) ◽  
pp. 2565-2569 ◽  
Author(s):  
Maria-Selma Arias ◽  
Yves G. Smeyers ◽  
Maria-Jose Fernandez ◽  
Nadine J. Smeyers ◽  
Enrique Galvez ◽  
...  
Keyword(s):  
Quantum Mechanical ◽  
Quantum Mechanical Calculations ◽  
Conformational Study ◽  
X Ray ◽  
X Ray Crystallography ◽  
Methyl Derivatives

scholarly journals Probing the Structure of [NiFeSe] Hydrogenase with QM/MM Computations

2020 ◽  
Vol 10 (3) ◽  
pp. 781 ◽  
Author(s):  
Samah Moubarak ◽  
N. Elghobashi-Meinhardt ◽  
Daria Tombolelli ◽  
Maria Andrea Mroginski
Keyword(s):  
Iron Oxidation ◽  
Structural Models ◽  
Oxidation States ◽  
Quantum Mechanical ◽  
Desulfovibrio Vulgaris ◽  
X Ray ◽  
X Ray Crystallography ◽  
Desulfovibrio Vulgaris Hildenborough ◽  
Optimized Geometries ◽  
Good Agreement

The geometry and vibrational behavior of selenocysteine [NiFeSe] hydrogenase isolated from Desulfovibrio vulgaris Hildenborough have been investigated using a hybrid quantum mechanical (QM)/ molecular mechanical (MM) approach. Structural models have been built based on the three conformers identified in the recent crystal structure resolved at 1.3 Å from X-ray crystallography. In the models, a diamagnetic Ni2+ atom was modeled in combination with both Fe2+ and Fe3+ to investigate the effect of iron oxidation on geometry and vibrational frequency of the nonproteic ligands, CO and CN-, coordinated to the Fe atom. Overall, the QM/MM optimized geometries are in good agreement with the experimentally resolved geometries. Analysis of computed vibrational frequencies, in comparison with experimental Fourier-transform infrared (FTIR) frequencies, suggests that a mixture of conformers as well as Fe2+ and Fe3+ oxidation states may be responsible for the acquired vibrational spectra.

scholarly journals Polymorphism in the structure of N-(5-methylthiazol-2-yl)-4-oxo-4H-chromene-3-carboxamide

2017 ◽  
Vol 73 (8) ◽  
pp. 1154-1161
Author(s):  
Ligia R. Gomes ◽  
John Nicolson Low ◽  
Fernando Cagide ◽  
Fernanda Borges
Keyword(s):  
Surface Analysis ◽  
Adenosine Receptors ◽  
Supramolecular Structure ◽  
Biological Activities ◽  
Major Change ◽  
Hirshfeld Surface ◽  
X Ray ◽  
Chromone Derivatives ◽  
X Ray Crystallography ◽  
Selective Ligand

Chromone derivatives have been extensively studied recently because of to their promising biological activities. The new title chromone–thiazole hybrid presented here, C14H10N2O3S, is a candidate as a selective ligand for adenosine receptors. The compound has been synthesized and characterized by the usual spectroscopic means (NMR and EM/IE) and its structure elucidated by X-ray crystallography, which revealed the presence of packing polymorphism. The two polymorphs (one with space group P21/n and one with P21/c) show slightly different conformations and the major change induced by crystallization regards the intramolecular contacts defining the supramolecular structure. Those differences been highlighted by Hirshfeld surface analysis mapped over d norm and ESP.

Novel Synthesis, Molecular Structure, and Theoretical Studies of Dispiro Compounds via Pseudo-eight-component Reaction

2014 ◽  
Vol 67 (11) ◽  
pp. 1656 ◽  
Author(s):  
Nourallah Hazeri ◽  
Mojtaba Lashkari ◽  
Santiago García-Granda ◽  
Laura Torre-Fernández
Keyword(s):  
Diels Alder ◽  
Quantum Mechanical ◽  
Theoretical Studies ◽  
Diastereoselective Synthesis ◽  
One Pot ◽  
X Ray ◽  
Complex Products ◽  
X Ray Crystallography ◽  
Novel Synthesis ◽  
The Stability

We have developed a diastereoselective synthesis of dispiro compounds through a one-pot domino pseudo-eight-component reaction of amines, aldehydes, and Meldrum’s acid. This method resulted in the generation of complex products with four stereocentres and involves formation of 10 new bonds. Quantum mechanical calculations were undertaken in order to determine the stability of the eight diastereomer structures of compound 4a. The crystal structure of 4k was determined by X-ray crystallography. Reaction mechanism can proceed through Knoevenagel, Aldol condensations, Diels-Alder cycloaddition, and Michael addition.

scholarly journals Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography

2018 ◽  
Author(s):  
Nate Yoder ◽  
Eric Gouaux
Keyword(s):  
Ion Channels ◽  
Divalent Cation ◽  
Binding Sites ◽  
Divalent Cations ◽  
Cation Binding ◽  
Ion Binding ◽  
X Ray ◽  
High Ph ◽  
X Ray Crystallography ◽  
Ion Binding Sites

AbstractAcid sensing ion channels (ASICs) are proton-gated ion channels that are members of the degenerin/epithelial sodium channel superfamily and are expressed throughout central and peripheral nervous systems. ASICs have been implicated in multiple physiological processes and are subject to numerous forms of endogenous and exogenous regulation that include modulation by Ca2+ and Cl− ions. However, the mapping of ion binding sites as well as a structure-based understanding of the mechanisms underlying ionic modulation of ASICs have remained elusive. Here we present ion binding sites of chicken ASIC1a in resting and desensitized states at high and low pH, respectively, determined by anomalous diffraction x-ray crystallography. The acidic pocket serves as a nexus for divalent cation binding at both low and high pH, while we observe divalent cation binding within the central vestibule on the resting channel at high pH only. Moreover, neutralization of residues positioned to coordinate divalent cations via individual and combined Glu to Gln substitutions reduced, but did not extinguish, modulation of proton-dependent gating by Ca2+. Additionally, we demonstrate that anion binding at the canonical thumb domain site is state-dependent and present a previously undetected anion site at the mouth of the extracellular fenestrations on the resting channel. Our results map anion and cation sites on ASICs across multiple functional states, informing possible mechanisms of modulation and providing a blueprint for the design of therapeutics targeting ASICs.

scholarly journals Enzymatic control of dioxygen binding and functionalization of the flavin cofactor

2018 ◽  
Vol 115 (19) ◽  
pp. 4909-4914 ◽  
Author(s):  
Raspudin Saleem-Batcha ◽  
Frederick Stull ◽  
Jacob N. Sanders ◽  
Bradley S. Moore ◽  
Bruce A. Palfey ◽  
...  
Keyword(s):  
Active Site ◽  
Rational Design ◽  
Quantum Mechanical ◽  
Organic Substrates ◽  
Quantum Mechanical Calculations ◽  
Critical Transition ◽  
Precise Positioning ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fine Tune

The reactions of enzymes and cofactors with gaseous molecules such as dioxygen (O2) are challenging to study and remain among the most contentious subjects in biochemistry. To date, it is largely enigmatic how enzymes control and fine-tune their reactions with O2, as exemplified by the ubiquitous flavin-dependent enzymes that commonly facilitate redox chemistry such as the oxygenation of organic substrates. Here we employ O2-pressurized X-ray crystallography and quantum mechanical calculations to reveal how the precise positioning of O2 within a flavoenzyme’s active site enables the regiospecific formation of a covalent flavin–oxygen adduct and oxygenating species (i.e., the flavin-N5-oxide) by mimicking a critical transition state. This study unambiguously demonstrates how enzymes may control the O2 functionalization of an organic cofactor as prerequisite for oxidative catalysis. Our work thus illustrates how O2 reactivity can be harnessed in an enzymatic environment and provides crucial knowledge for future rational design of O2-reactive enzymes.

Difference Fourier Analysis of Glucose Embedded and Frozen Hydrated Purple Membrane

1982 ◽  
Vol 40 ◽  
pp. 74-75
Author(s):  
Jules S. Jaffe ◽  
Robert M. Glaeser
Keyword(s):  
Purple Membrane ◽  
Data Set ◽  
High Resolution Data ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fourier Techniques ◽  
Versus Protein ◽  
The Difference ◽  
Difference Fourier ◽  
Ideal Method

Although difference Fourier techniques are standard in X-ray crystallography it has only been very recently that electron crystallographers have been able to take advantage of this method. We have combined a high resolution data set for frozen glucose embedded Purple Membrane (PM) with a data set collected from PM prepared in the frozen hydrated state in order to visualize any differences in structure due to the different methods of preparation. The increased contrast between protein-ice versus protein-glucose may prove to be an advantage of the frozen hydrated technique for visualizing those parts of bacteriorhodopsin that are embedded in glucose. In addition, surface groups of the protein may be disordered in glucose and ordered in the frozen state. The sensitivity of the difference Fourier technique to small changes in structure provides an ideal method for testing this hypothesis.

3-D reconstruction of molecular shape from microcrystal thin sections

1983 ◽  
Vol 41 ◽  
pp. 748-749
Author(s):  
S. Cusack ◽  
J.-C. Jésior
Keyword(s):  
Three Dimensional ◽  
Molecular Shape ◽  
Biological Molecules ◽  
Fourier Space ◽  
Single Particles ◽  
Thin Sections ◽  
Standard Methods ◽  
X Ray ◽  
X Ray Crystallography ◽  
Dimensional Reconstruction

Three-dimensional reconstruction techniques using electron microscopy have been principally developed for application to 2-D arrays (i.e. monolayers) of biological molecules and symmetrical single particles (e.g. helical viruses). However many biological molecules that crystallise form multilayered microcrystals which are unsuitable for study by either the standard methods of 3-D reconstruction or, because of their size, by X-ray crystallography. The grid sectioning technique enables a number of different projections of such microcrystals to be obtained in well defined directions (e.g. parallel to crystal axes) and poses the problem of how best these projections can be used to reconstruct the packing and shape of the molecules forming the microcrystal.Given sufficient projections there may be enough information to do a crystallographic reconstruction in Fourier space. We however have considered the situation where only a limited number of projections are available, as for example in the case of catalase platelets where three orthogonal and two diagonal projections have been obtained (Fig. 1).

Electron microscopy of rabbit FC crystals

1983 ◽  
Vol 41 ◽  
pp. 730-731
Author(s):  
Robert A. Grant ◽  
Laura L. Degn ◽  
Wah Chiu ◽  
John Robinson
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
High Resolution Electron Microscopy ◽  
Molecular Replacement ◽  
X Ray ◽  
X Ray Crystallography ◽  
Resolution Electron ◽  
Replacement Technique ◽  
Hydrated Crystal ◽  
Molecular Structure Analysis

Proteolytic digestion of the immunoglobulin IgG with papain cleaves the molecule into an antigen binding fragment, Fab, and a compliment binding fragment, Fc. Structures of intact immunoglobulin, Fab and Fc from various sources have been solved by X-ray crystallography. Rabbit Fc can be crystallized as thin platelets suitable for high resolution electron microscopy. The structure of rabbit Fc can be expected to be similar to the known structure of human Fc, making it an ideal specimen for comparing the X-ray and electron crystallographic techniques and for the application of the molecular replacement technique to electron crystallography. Thin protein crystals embedded in ice diffract to high resolution. A low resolution image of a frozen, hydrated crystal can be expected to have a better contrast than a glucose embedded crystal due to the larger density difference between protein and ice compared to protein and glucose. For these reasons we are using an ice embedding technique to prepare the rabbit Fc crystals for molecular structure analysis by electron microscopy.

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