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1.
短杆菌肽A-DMPC通道内离子输运的分子动力学模拟 总被引:2,自引:0,他引:2
用最近提出的构建膜体系初始构象的有效方法 ,构建了在DMPC脂膜环境下短杆菌肽A通道模型 (GA -DMPC)。通过对Na 、Ca2 、Cl-三种不同离子在GA -DMPC通道内不同位置的分子动力学模拟 ,研究离子在通道内输运过程中与通道及通道内水分子的相互作用 ,从分子动力学的角度阐明离子在通道内的输运机制。主要计算结果表明 :(1)离子在通道内的输运使GA的构象发生变化 ,GA的柔性是离子在通道内通透的重要因素 ;(2)Cl- 离子可扩大通道半径 ,Na 离子和Ca2 离子则减小通道半径。Cl-离子不能在GA通道内通透 ;(3)离子的出现使通道内水分子的偶极方向发生变化。上述结果均与实验相符。 相似文献
2.
O.V. Krasilnikov J.B. Da Cruz L.N. Yuldasheva W.A. Varanda R.A. Nogueira 《The Journal of membrane biology》1998,161(1):83-92
This paper describes a new approach to evaluate the inner structure (including a main constriction and its localization)
of the water lumen of an ion channel. The method is based on the determination of channel filling by different nonelectrolyte
molecules through each side of an ion channel. The method has two characteristic features that make its use attractive: (i)
the possibility to ascertain the existence, localization and size of a narrow part inside an ion channel water lumen and (ii)
the chances to determine the maximal size of both entrances of an ion channel and to obtain additional information about the
geometry of its water lumen at the same time. Determinations were made on colicin Ia ion channels inserted into planar lipid
bilayers. This channel was chosen because there is an apparent contradiction between its low single channel conductance and
the large diameter of its water lumen. Our results show that the water lumen of the colicin Ia channel has a funnel-like structure
with a small trans-entrance, with a diameter of about 1.0 nm, and a large cis-entrance, with a diameter of approximately 1.8 nm. A constriction with a diameter of approximately 0.7 nm is shown to be
located close to the trans-entrance of the channel. The method can also be applied to patch clamp studies of single ion channels.
Received: 20 February 1997/Revised: 19 August 1997 相似文献
3.
A new fluorescent chemosensor for cadmium(II) based on a pyrene‐appended piperidone derivative and its β‐cyclodextrin complex
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Sumathi Poomalai Tamil Selvan Govindaraj Suganthi Soundrapandian Mosae Selvakumar Paulraj Israel Vijayaraj Muthu Vijayan Enoch 《Luminescence》2018,33(3):538-544
We report, in this article, a piperidin‐4‐one derivative carrying pyrenyl fluorescent reporter groups which acts as a Cd2+ ion sensor. The compound is synthesized and characterized using IR and NMR spectral techniques. The compound forms an inclusion complex with β‐cyclodextrin. It selectively binds to Cd2+ ions in water and aqueous β‐cyclodextrin media. The stoichiometry of the host–guest complex of the compound with β‐cyclodextrin is 1:2. The ligand–metal ion binding stoichiometry is 1:1 both in water and in β‐cyclodextrin. The linear concentration range of detection of the metal ion is reported. Cyclodextrin complex formation does not affect the metal ion selectivity of the compound. 相似文献
4.
Alexander V. Nemukhin Ilya A. Kaliman Alexander A. Moskovsky 《Journal of molecular modeling》2009,15(8):1009-1012
The results of potential of mean force (PMF) calculations for the distinct stages of proton conduction through the gramicidin
A channel, including proton migration, reorientation of the water file and negative ion defect migration, are presented. The
negative ion defect migration mechanism was hypothesized in experimental studies but was not considered previously in molecular
dynamics simulations. The model system consisted of the peptide chains constructed on the base of the structure PDBID:1JNO,
the inner file of nine water molecules and external clusters of water molecules placed at both ends of the channel. Potential
energy functions were computed with the CHARMM/PM6/TIP3P parameters. The results obtained for proton migration and water file
reorientation are basically consistent with those reported previously by Pómès and Roux (Biophys J 82:2304, 2002) within the similar approach. For the newly considered mechanism of negative ion defect migration from the channel center
to the end of the water file we obtain the energy 3.8 kcal mol−1 which is not considerably different from the activation energy of water reorientation, 5.4 kcal mol−1. Therefore this mechanism may principally compete for the rate-limiting step in proton conduction in gramicidin. 相似文献
5.
Song Hi Lee 《Molecular simulation》2014,40(4):335-340
We present results of molecular dynamics simulations for diffusion of Na+ ion in water-filled carbon nanotubes (CNTs) at 25°C using the extended simple point charge water potential. Simulation results indicate the general trend that the diffusion coefficients of Na+ ion and water molecule in CNTs decrease with an increase in water density and are larger than those in the bulk solution. The average potential energies of ion–water and water–water, the radial distribution functions, the hydration numbers and the residence times of the hydrated water molecules are discussed. The classical solventberg picture describes Na+ ion in water adequately for systems with the small values of diffusion coefficients. 相似文献
6.
Streaming potentials in gramicidin channels measured with ion-selective microelectrodes. 总被引:1,自引:0,他引:1
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Streaming potentials have been measured for gramicidin channels with a new method employing ion-selective microelectrodes. It is shown that ideally ion-selective electrodes placed at the membrane surface record the true streaming potential. Using this method for ion concentrations below 100 mM, approximately seven water molecules are transported whenever a sodium, potassium, or cesium ion, passes through the channel. This new method confirms earlier measurements (Rosenberg, P.A., and A. Finkelstein. 1978. Interaction of ions and water in gramicidin A channels. J. Gen. Physiol. 72:327-340) in which the streaming potentials were calculated as the difference between electrical potentials measured in the presence of gramicidin and in the presence of the ion carriers valinomycin and nonactin. 相似文献
7.
J Wu 《Biophysical journal》1991,60(1):238-251
Ionic permeation in the selectivity filter of ion channels is analyzed by a microscopic model based on molecular kinetic theory. The energy and flux equations are derived by assuming that: (a) the selectivity filter is formed by a symmetrical array of carbonyl groups; (b) ion movement is near the axis of the channel; (c) a fraction of water molecules is separated from the ion while it moves across the selectivity filter; (d) the applied voltage drops linearly across the selectivity filter; (e) ions move independently. Energy profiles, single channel conductances, and the degree of hydration of K+ in a hypothetical K+ channel are examined by varying the following microscopic parameters: ion radius and mass, channel radius, number of effective water dipoles, and number of carbonyl groups. The i-V curve is linear up to +/- 170 mV. If the positions of energy maxima and minima are fixed, this linear range is reduced to +/- 50 mV. Channel radius and ion-water interactions are found to be two major channel structural determinants for selectivity sequences. Both radius and mass of an ion are important in selectivity mediated by these interactions. The theory predicts a total of 15 possible kinetic selectivity sequences for alkali cations in ion channels with a single selectivity filter. 相似文献
8.
Summary The response of caudal neurosecretory cells in Salvelinus fontinalis to exposure to media in which one ion (Na, K, Mg, Ca and Cl) was either selectively enriched or depleted was evaluated by morphometric criteria. Morphological changes indicating stimulation of synthetic activity were observed: exposure to sea water with low potassium concentration was the most efficacious in inducing the increase in the average diameter of caudal cells and the number of nucleoli for both cells with lobed and with nonlobed nuclei. The proportion of cells with lobed nuclei was also increased. To a lesser degree and in decreasing order, experimental milieu with modified magnesium contents, either fresh water enriched in this ion or seawater depleted of the same ion, and fresh water enriched in calcium also resulted in significant increases in cell diameter and the number of nucleoli.The two cytological cell types, viz cells with non-lobed nuclei or cells with lobed nuclei, are interpreted as being linked to different levels of neurosecretory activity.Supported by NSERC (Canada) 相似文献
9.
At present, the three‐dimensional structure of the multimeric paracellular claudin pore is unknown. Using extant biophysical data concerning the size of the pore and permeation of water and cations through it, two three‐dimensional models of the pore are constructed in silico. Molecular Dynamics (MD) calculations are then performed to compute water and sodium ion permeation fluxes under the influence of applied hydrostatic pressure. Comparison to experiment is made, under the assumption that the hydrostatic pressure applied in the simulations is equivalent to osmotic pressure induced in experimental measurements of water/ion permeability. One model, in which pore‐lining charged is distributed evenly over a selectivity filter section 10–16 Å in length, is found to be generally consistent with experimental data concerning the dependence of water and ion permeation on channel pore diameter, pore length, and the sign and magnitude of pore lining charge. The molecular coupling mechanism between water and ion flow under conditions where hydrostatic pressure is applied is computationally elucidated. Proteins 2016; 84:305–315. © 2016 Wiley Periodicals, Inc. 相似文献
10.
11.
The effect of vanadate (orthovanadate, VO4-) on water and ion transport was studied in rat jejunum. Water transport was tested by single-pass perfusion in vivo and ion fluxes by the Ussing-chamber technique in vitro. The results suggest that vanadate has two actions on ion and water transport: At low concentrations (10(-4) M) it causes Cl-, Na+ and water secretion by stimulation of adenylate cyclase; At higher concentrations (10(-3) and 10(-2) M) it decreases net absorption of Na+ and Cl- by inhibition of (Na+ + K+)-ATPase. 相似文献
12.
Danks HV 《Journal of insect physiology》2000,46(6):837-852
Many of the mechanisms used by active insects to maintain water balance are not available to dormant individuals. Physiological and biochemical mechanisms of dehydration tolerance and resistance in dormant insects and some other invertebrates are reviewed, as well as linkages of dehydration with energy use and metabolism, with cold hardiness, and with diapause. Many dormant insects combine several striking adaptations to maintain water balance that-in addition to habitat choice-may include especially reduction of body water content, decreased cuticular permeability, absorption of water vapour, and tolerance of low body water levels. Many such features require energy and hence that metabolism, albeit much reduced, continues during dormancy. Four types of progressively dehydrated states are recognized: water is managed internally by solute or ion transport; relatively high concentrations of solutes modify the behaviour of water in solutions; still higher concentrations of certain carbohydrates lead to plasticized rubbers or glasses with very slow molecular kinetics; and anhydrobiosis eliminates metabolism. 相似文献
13.
Molecular dynamics simulation of cation motion in water-filled gramicidinlike pores. 总被引:4,自引:4,他引:0
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A model calculation is carried out to study the potential energy profile of a sodium ion with several water molecules inside a simplified model of the gramicidin ion channel. The sodium ion is treated as a Lennard-Jones sphere with a point charge at its center. The Barnes polarizable water model is used to mimic the water molecules. A polarizable and deformable gramicidinlike channel is constructed based on the model obtained by Koeppe and Kimura. Potential minima and saddle points are located and the static energy barriers are computed. The potential minima at the two mouths of the channel exhibit an aqueous solvation structure very different from that at any of the interior minima. These sites are approximately 23.6 and 24.4 A apart for binding of a sodium ion and a cesium ion, respectively. Ionic motion from these exterior sites to the first interior minimum requires substantial rearrangement of the waters of solvation; this rearrangement may be the hydration/dehydration step in ionic permeation through the channel. Based on these results, a mechanism by which the sodium ion moves from the exterior binding site to the interior of the channel is proposed. Our model channel accommodates about eight water molecules and the transport of the ion and water within the channel is found to be single file. Results of less extensive calculations for Cs+ and Li+ ions in a channel with or without water are also reported. 相似文献
14.
Ion leakage through transient water pores in protein-free lipid membranes driven by transmembrane ionic charge imbalance 总被引:1,自引:0,他引:1
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We have employed atomic-scale molecular dynamics simulations to address ion leakage through transient water pores in protein-free phospholipid membranes. Our results for phospholipid membranes in aqueous solution with NaCl and KCl salts show that the formation of transient water pores and the consequent ion leakage can be induced and be driven by a transmembrane ionic charge imbalance, an inherent feature in living cells. These processes take place if the gradient is large enough to develop a sufficiently significant potential difference across the membrane. The transport of cations and anions through the water pores is then seen; it discharges the transmembrane potential, considerably reduces the size of a water pore, and makes the water pore metastable, leading eventually to its sealing. The ion transport is found to be sensitive to the type of ions. It turns out that Na(+) and Cl(-) ions leak through a membrane at approximately the same ratio despite the fact that Na(+) ions are expected to experience a lower potential barrier for the permeation through the pore. This is because of strong interactions of sodium ions with the carbonyl region of a phospholipid membrane as well as with lipid headgroups forming pore "walls," considerably slowing down the permeation of sodium ions. In contrast, we observed a pronounced selectivity of a phospholipid membrane to the permeation of potassium ions as compared to chloride ions: Potassium ions, being larger than sodium ions, interact only weakly with phospholipid headgroups, so that these interactions are not able to compensate for a large difference in free-energy barriers for permeation of K(+) and Cl(-) ions. These findings are found to be robust to a choice of force-field parameters for ions (tested by Gromacs and Charmm force-fields for ions). What is more, a potassium ion is found to be able to permeate a membrane along an alternate, "water-defect-mediated" pathway without actual formation of a pore. The "water-defect-mediated" leakage involves formation of a single water defect only and is found to be at least one order of magnitude faster than the pore-mediated ion leakage. 相似文献
15.
The effect of channel length on the barrier for potassium ion permeation through single-file channels has been studied by means of all-atom molecular dynamics simulations. Using series of peptidic gramicidin-like and simplified ring-structured channels, both embedded in model membranes, we obtained two distinct types of behavior: saturation of the central free energy barriers for peptidic channels and a linear increase in simplified ring-structured channels with increasing channel length. The saturation of the central free energy barrier for the peptidic channels occurs at relatively short lengths, and it is correlated with the desolvation from the bulk water. Remarkably, decomposition of free energy barriers into enthalpic and entropic terms reveals an entropic cost for ion permeation. Furthermore, this entropic cost dominates the ion permeation free energy barrier, since the corresponding free energy contribution is higher than the enthalpic barrier. We conclude that the length dependence of the free energy is enthalpy-dominated, but the entropy is the major contribution to the permeation barrier. The decrease in rotational water motion and the reduction of channel mobility are putative origins for the overall entropic penalty. 相似文献
16.
Laser Flash Photolysis (LFP) experiments carried out on 2-azidofluorene in aqueous systems generate 2-fluorenyl nitrenium ion (lambda(max) = 450 nm) which decays with first order rate constant and is quenched with 2'-deoxyguanosine originating an intermediate, namely the C8 adduct of 2-fluorenyl nitrenium ion, with bimolecular rate constant in the order of 1.3 x 10(9) M(-1) s(-1) in pure water. This intermediate very likely mimics the intermediate formed from carcinogens (i.e.: arylnitrenium ions formed through metabolic activation pathways from aminoaromatic substrates) and DNA rests in vivo. Solvent effects demonstrate and support the further stabilization of this intermediate (with respect to fluorenyl nitrenium ion) through hydrogen bonding as compared to other probe systems, and accounts for the enhanced metabolic carcinogenecity observed for this type of compounds. Diverse solvent systems, such as mixtures of water with acetonitrile, 1,1,1-trifluoroethanol, and 1,1,1,3,3,3-hexafluoroisopropanol, are used to interpret solvent-complex interactions. 相似文献
17.
K+ ions seemingly permeate K-channels rapidly because channel binding sites mimic coordination of K+ ions in water. Highly selective ion discrimination should occur when binding sites form rigid cavities that match K+, but not the smaller Na+, ion size or when binding sites are composed of specific chemical groups. Although conceptually attractive, these views cannot account for critical observations: 1), K+ hydration structures differ markedly from channel binding sites; 2), channel thermal fluctuations can obscure sub-Angstr?m differences in ion sizes; and 3), chemically identical binding sites can exhibit diverse ion selectivities. Our quantum mechanical studies lead to a novel paradigm that reconciles these observations. We find that K-channels utilize a "phase-activated" mechanism where the local environment around the binding sites is tuned to sustain high coordination numbers (>6) around K+ ions, which otherwise are rarely observed in liquid water. When combined with the field strength of carbonyl ligands, such high coordinations create the electrical scenario necessary for rapid and selective K+ partitioning. Specific perturbations to the local binding site environment with respect to strongly selective K-channels result in altered K+/Na+ selectivities. 相似文献
18.
Gramicidin A pores are permeable to water and small monovalent cations. For K, Rb, and Cs there is good evidence from conductances and permeability ratios that a second ion can enter a pore already occupied by another, but for Na this evidence is inconclusive and comparison of tracer fluxes and single channel conductances suggests that second ion entries are prohibited. Partly as a result of the complications of second ion entry there have been widely differing estimates for the dissociation constants for the first ion in the channel. Dani and Levitt (1981, Biophys. J.
35: 485–499) introduced a method for calculating ion binding constants from simultaneous measurements of water fluxes and membrane conductance. They found no evidence for second ion binding and calculated dissociation constants of 115 mm for Li, 69 mm for K, and 2 mm for Tl. It is shown here that the two-ion, four-state model predicts a dependence of water permeability on ion concentration that is difficult to distinguish from the predictions of block by a single ion. Using a modified technique that allows measurement of higher conductances, the first ion dissociation constants have been determined as 80 mm for Na, 40 mm for Rb and 15 mm for Cs. These values and those of Dani and Levitt fall in a smooth sequence. The dissociation constant for Cs is consistent with single channel conductances and flux ratios. There is a discrepancy between this constant for Na and the value, 370 mm, calculated from the single channel conductances and the assumption that a second ion cannot enter or affect an occupied pore. The dissociation constant for Rb is intermediate between those for K and Cs whereas tracer flux measurements (Schagina, Grinfeldt & Lev, 1983. J. Membrane Biol.
73: 203–216) have suggested that Rb interacts much more strongly with the channel than Cs.We should like to thank the National Grid plc, for the grant which supported K.-W.W., the Wellcome Trust for a visiting Fellowship for S.T. in Cambridge, and the Cambridge Society of Bombay which supported S.B.H. in Bombay. 相似文献
19.
S M Saparov D Kozono U Rothe P Agre P Pohl 《The Journal of biological chemistry》2001,276(34):31515-31520
The aquaporin-1 (AQP1) water channel protein is known to facilitate the rapid movement of water across cell membranes, but a proposed secondary role as an ion channel is still unsettled. Here we describe a method to simultaneously measure water permeability and ion conductance of purified human AQP1 after reconstitution into planar lipid bilayers. Water permeability was determined by measuring Na(+) concentrations adjacent to the membrane. Comparisons with the known single channel water permeability of AQP1 indicate that the planar lipid bilayers contain from 10(6) to 10(7) water channels. Addition of cGMP induced ion conductance in planar bilayers containing AQP1, whereas cAMP was without effect. The number of water channels exceeded the number of active ion channels by approximately 1 million-fold, yet p-chloromethylbenzenesulfonate inhibited the water permeability but not ion conductance. Identical ion channel parameters were achieved with AQP1 purified from human red blood cells or AQP1 heterologously expressed in Saccharomyces cerevisae and affinity purified with either N- or C-terminal poly-histidine tags. Rp-8-Br-cGMP inhibited all of the observed conductance levels of the cation selective channel (2, 6, and 10 pS in 100 mm Na(+) or K(+)). Deletion of the putative cGMP binding motif at the C terminus by introduction of a stop codon at position 237 yielded a truncated AQP1 protein that was still permeated by water but not by ions. Our studies demonstrate a method for simultaneously measuring water permeability and ion conductance of AQP1 reconstituted into planar lipid bilayers. The ion conductance occurs (i) through a pathway distinct from the aqueous pathway, (ii) when stimulated directly by cGMP, and (iii) in only an exceedingly small fraction of AQP1 molecules. 相似文献
20.
Polson C Sarkar P Incledon B Raguvaran V Grant R 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,785(2):263-275
Four categories of protein precipitation techniques (organic solvent, acid, salt and metal ion) were tested in plasma using spectrophotometry to assess protein removal efficiency across a range of volumes, species and lots. Acetonitrile, trichloroacetic acid (TCA) and zinc sulfate were found to be optimal at removing protein in their categories (>96, 92 and 91% protein precipitation efficiency at a 2:1 ratio of precipitant to plasma, respectively). A post-column infusion LC-MS/MS system was used to assess ionization effect of a protein-bound drug caused by the endogenous components remaining after using various protein precipitants. The extent of ionization effect varied with mobile phase (-20 to 93%), protein precipitant (0.3-86%), but only slightly with species (86-93%). The optimal bioanalytical methodologies for removal of plasma proteins and minimal ionization effect for the probe molecule in positive ion turboionspray LC-MS/MS involve the use of TCA for precipitation with mobile phases consisting of either pure organic solvents (methanol:water or acetonitrile:water) or precipitation with all of the mass spectrometer compatible precipitants evaluated with a methanol:aqueous 0.1% formic acid mobile phase. 相似文献