Recent Submissions

  • Journal Article

    Effect of Adhesion and Substrate Elasticity on Neutrophil Extracellular Trap Formation 

    Erpenbeck, Luise; Gruhn, Antonia Luise; Kudryasheva, Galina; Günay, Gökhan; Meyer, Daniel; Busse, Julia; Neubert, Elsa; Schön, Michael P.; Rehfeldt, Florian; Kruss, Sebastian
    Frontiers in Immunology 2019; 10: Art. 2320
    Neutrophils are the most abundant type of white blood cells. Upon stimulation, they are able to decondense and release their chromatin as neutrophil extracellular traps (NETs). This process (NETosis) is part of immune defense mechanisms but also plays an important role in many chronic and inflammatory diseases such as atherosclerosis, rheumatoid arthritis, diabetes, and cancer. For this reason,much effort has been invested into understanding biochemical signaling pathways in NETosis. However, the impact of the mechanical micro-environment and adhesion on NETosis is not well-understood. Here, we studied how adhesion and especially substrate elasticity affect NETosis. We employed polyacrylamide (PAA) gels with distinctly defined elasticities (Young’s modulus E) within the physiologically relevant range from 1 to 128 kPa and coated the gels with integrin ligands (collagen I, fibrinogen). Neutrophils were cultured on these substrates and stimulated with potent inducers of NETosis: phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS). Interestingly, PMA-induced NETosis was neither affected by substrate elasticity nor by different integrin ligands. In contrast, for LPS stimulation, NETosis rates increased with increasing substrate elasticity (E > 20 kPa). LPS-induced NETosis increased with increasing cell contact area, while PMA-induced NETosis did not require adhesion at all. Furthermore, inhibition of phosphatidylinositide 3 kinase (PI3K), which is involved in adhesion signaling, completely abolished LPS-induced NETosis but only slightly decreased PMA-induced NETosis. In summary, we show that LPS-induced NETosis depends on adhesion and substrate elasticity while PMA-induced NETosis is completely independent of adhesion.
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  • Journal Article

    A critical comparison of neural network potentials for molecular reaction dynamics with exact permutation symmetry 

    Li, Jun; Song, Kaisheng; Behler, Jörg
    Physical Chemistry Chemical Physics 2019; 21(19) p.9672-9682
    The availability of accurate full-dimensional potential energy surfaces (PESs) is a mandatory condition for efficient computer simulations of molecular systems. Much effort has been devoted to developing reliable PESs with physically sound properties, such as the invariance of the energy with respect to the permutation of chemically identical atoms. In this work, we compare the performance of four neural network (NN)-based approaches with a rigorous permutation symmetry for fitting five typical reaction systems: OH + CO, H + H2S, H + NH3, H + CH4 and OH + CH4. The methods can be grouped into two categories, invariant polynomial based NNs and high-dimensional NN potentials (HD-NNPs). For the invariant polynomial based NNs, three types of polynomials, permutation invariant polynomials (PIPs), non-redundant PIPs (NRPIPs) and fundamental invariants (FIs), are used in the input layer of the NN. In HD-NNPs, the total energy is the sum of atomic contributions, each of which is given by an individual atomic NN with input vectors consisting of sets of atom-centered symmetry functions. Our results show that all methods exhibit a similar level of accuracy for the energies with respect to ab initio data obtained at the explicitly correlated coupled cluster level of theory (CCSD(T)-F12a). The HD-NNP method allows study of systems with larger numbers of atoms, making it more generally applicable than invariant polynomial based approaches, which in turn are computationally more efficient for smaller systems. To illustrate the applicability of the obtained potentials, quasi-classical trajectory calculations have been performed for the OH + CH4 → H2O + CH3 reaction to reveal its complicated mode specificity.
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  • Journal Article

    PDB2INS: bridging the gap between small-molecule and macromolecular refinement 

    Lübben, Anna V.; Sheldrick, George M.
    Journal of Applied Crystallography 2019; 52(3) p.669-673
    The open-source Python program PDB2INS is designed to prepare a .ins file for refinement with SHELXL [Sheldrick (2015). Acta Cryst. C71, 3-8], taking atom coordinates and other information from a Protein Data Bank (PDB)-format file. If PDB2INS is provided with a four-character PDB code, both the PDB file and the accompanying mmCIF-format reflection data file (if available) are accessed via the internet from the PDB public archive [Read et al. (2011). Structure, 19, 1395-1412] or optionally from the PDB_REDO server [Joosten, Long, Murshudov & Perrakis (2014). IUCrJ, 1, 213-220]. The SHELX-format .ins (refinement instructions and atomic coordinates) and .hkl (reflection data) files can then be generated without further user intervention, appropriate restraints etc. being added automatically. PDB2INS was tested on the 23 974 X-ray structures deposited in the PDB between 2008 and 2018 that included reflection data to 1.7 Å or better resolution in a recognizable format. After creating the two input files for SHELXL without user intervention, ten cycles of conjugate-gradient least-squares refinement were performed. For 96% of these structures PDB2INS and SHELXL completed successfully without error messages.
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  • Journal Article

    Fluorinated nanobodies for targeted molecular imaging of biological samples using nanoscale secondary ion mass spectrometry 

    Kabatas, Selda; Agüi-Gonzalez, Paola; Hinrichs, Rena; Jähne, Sebastian; Opazo, Felipe; Diederichsen, Ulf; Rizzoli, Silvio O.; Phan, Nhu T. N.
    Journal of Analytical Atomic Spectrometry 2019; 34(6) p.1083-1087
    Molecular imaging of targeted large biomolecules has been restricted in SIMS due to the limited number of probes containing SIMS-detectable isotopes. We introduce here new 19F-containing molecules that can be conjugated in a site-specific manner to nanobodies able to recognize fluorescent proteins (FPs) or mouse immunoglobulins (Igs). In this work, we demonstrate that it is possible to use the 19F-nanobodies to reveal the location of several cellular proteins previously tagged with FPs or Igs. This enables specific bio-imaging in SIMS for a vast repertoire of biomolecules, offering new opportunities to study specific structural and functional molecular interactions in biological specimens.
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  • Journal Article

    Shock wave and modelling study of the dissociation pathways of (C2F5)3N 

    Cobos, C. J.; Hintzer, K.; Sölter, L.; Tellbach, E.; Thaler, A.; Troe, J.
    Physical Chemistry Chemical Physics 2019; 21(19) p.9785-9792
    The thermal decomposition of perfluorotriethylamine, (C2F5)3N, was investigated in shock waves by monitoring the formation of CF2. Experiments were performed over the temperature range of 1120-1450 K with reactant concentrations between 100 and 1000 ppm of (C2F5)3N in the bath gas Ar and with [Ar] in the range of (0.7-5.5) × 10-5 mol cm-3. The experiments were accompanied by quantum-chemical calculations of the energies of various dissociation paths and by rate calculations, in particular for the dissociation of C2F5via C2F5 → CF3 + CF2. The overall reaction can proceed in different ways, either by a sequence of successive C-N bond ruptures followed by fast C2F5 decompositions, or by a sequence of alternating C-C and C-N bond ruptures. A cross-over between the two pathways can also take place. At temperatures below about 1300 K, yields of less than one CF2 per (C2F5)3N decomposed were observed. On the other hand, at temperatures around 2000 K, when besides the parent molecule, CF3 also dissociates, yields of six CF2 per (C2F5)3N decomposed were measured. The rate-delaying steps of the dissociation mechanism at intermediate temperatures were suggested to be the processes (C2F5)NCF2 → (C2F5)N + CF2 and (CF2)N → N + CF2. The reduction of the CF2 yields at low temperatures was tentatively attributed to a branching of the mechanism at the level of (C2F5)2NCF2, from where the cyclic final product perfluoro-N-methylpyrrolidine, (C4F8)NCF3, is formed which was identified in earlier work from the literature
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  • Journal Article

    5-(Cyano)dibenzothiophenium Triflate: A Sulfur-Based Reagent for Electrophilic Cyanation and Cyanocyclizations 

    Li, Xiangdong; Golz, Christopher; Alcarazo, Manuel
    Angewandte Chemie International Edition 2019; 58(28) p.9496-9500
    The synthesis of 5-(cyano)dibenzothiophenium triflate 9, prepared by activation of dibenzo[b,d]thiophene-5-oxide with Tf2 O and subsequent reaction with TMSCN is reported, and its reactivity as electrophilic cyanation reagent evaluated. The scalable preparation, easy handling and broad substrate scope of the electrophilic cyanation promoted by 9, which includes amines, thiols, silyl enol ethers, alkenes, electron rich (hetero)arenes and polyaromatic hydrocarbons, illustrate the synthetic potential of this reagent. Importantly, Lewis acid activation of the reagent is not required for the transfer process. We additionally report herein biomimetic cyanocyclization cascade reactions, which are not promoted by typical electrophilic cyanation reagents, demonstrating the superior ability of 9 to trigger challenging transformations.
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  • Journal Article

    Isolation of base stabilized fluoroborylene and its radical cation 

    Sarkar, Samir Kumar; Siddiqui, Mujahuddin M.; Kundu, Subrata; Ghosh, Munmun; Kretsch, Johannes; Stollberg, Peter; Herbst-Irmer, Regine; Stalke, Dietmar; Stückl, A. Claudia; Schwederski, Brigitte; et al.
    Kaim, WolfgangGhorai, SagarJemmis, Eluvathingal D.Roesky, Herbert W.
    Dalton Transactions 2019; 48(24) p.8551-8555
    Herein, we report the synthesis and characterization of the metal free low valent fluoroborylene [(Me-cAAC)2BF] (1) stabilized by cyclic (alkyl)(amino) carbene (cAAC). The fluoroborylene 1 is obtained by the reductive defluorination of Me-cAAC:BF3 with 2.0 equivalents of KC8 in the presence of 1.0 equivalent of Me-cAAC. Due to its highly electron rich nature, 1 underwent one-electron oxidation with 1.0 equivalent of lithium tetrakis(pentafluorophenyl)borate [LiB(C6F5)4] to form the radical cation [(Me-cAAC)2BF]˙+[B(C6F5)4]- (2). DFT studies suggested that the lone pair of electrons is localized on the boron atom in 1, which explains its unprecedented reactivity. Both compounds 1 and 2 were characterized by X-ray crystallography. The radical cation 2 was studied by EPR spectroscopy.
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  • Journal Article

    On the Competition Between Electron Autodetachment and Dissociation of Molecular Anions 

    Marowsky, Gerd; Troe, Jürgen; Viggiano, Albert A.
    Journal of The American Society for Mass Spectrometry
    We treat the competition between autodetachment of electrons and unimolecular dissociation of excited molecular anions as a rigid-/loose-activated complex multichannel reaction system. To start, the temperature and pressure dependences under thermal excitation conditions are represented in terms of falloff curves of separated single-channel processes within the framework of unimolecular reaction kinetics. Channel couplings, caused by collisional energy transfer and "rotational channel switching" due to angular momentum effects, are introduced afterward. The importance of angular momentum considerations is stressed in addition to the usual energy treatment. Non-thermal excitation conditions, such as typical for chemical activation and complex-forming bimolecular reactions, are considered as well. The dynamics of excited SF6- anions serves as the principal example. Other anions such as CF3- and POCl3- are also discussed.
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  • Journal Article

    Chirality enriched carbon nanotubes with tunable wrapping via corona phase exchange purification (CPEP) 

    Nißler, Robert; Mann, Florian A.; Preiß, Helen; Selvaggio, Gabriele; Herrmann, Niklas; Kruss, Sebastian
    Nanoscale 2019; 11(23) p.11159-11166
    Single-walled carbon nanotubes (SWCNTs) have unique photophysical properties and serve as building blocks for biosensors, functional materials and devices. For many applications it is crucial to use chirality-pure SWCNTs, which requires sophisticated processes. Purification procedures such as wrapping by certain polymers, phase separation, density gradient centrifugation or gel chromatography have been developed and yield distinct SWCNT species wrapped by a specific polymer or surfactant. However, many applications require a different organic functionalization (corona) around the SWCNTs instead of the one used for the purification process. Here, we present a novel efficient and straightforward process to gain chirality pure SWCNTs with tunable functionalization. Our approach uses polyfluorene (PFO) polymers to enrich certain chiralities but the polymer is removed again and finally exchanged to any desired organic phase. We demonstrate this concept by dispersing SWCNTs in poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(6,6'-{2,2'-bipyridine})] (PFO-BPy), which is known to preferentially solubilize (6,5)-SWCNTs. Then PFO-BPy is removed and recycled, while letting the SWCNTs adsorb/agglomerate on sodium chloride (NaCl) crystals, which act as a toluene-stable but water-soluble filler material. In the last step these purified SWCNTs are redispersed in different polymers, surfactants and ssDNA. This corona phase exchange purification (CPEP) approach was also extended to other PFO variants to enrich and functionalize (7,5)-SWCNTs. CPEP purified and functionalized SWCNTs display monodisperse nIR spectra, which are important for fundamental studies and applications that rely on spectral changes. We show this advantage for SWCNT-based nIR fluorescent sensors for the neurotransmitter dopamine and red-shifted sp3 defect peaks . In summary, CPEP makes use of PFO polymers for chirality enrichment but provides access to chirality enriched SWCNTs functionalized in any desired polymer, surfactant or biopolymer.
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  • Journal Article

    Fluorinated nanobodies for targeted molecular imaging of biological samples using nanoscale secondary ion mass spectrometry 

    Kabatas, Selda; Agüi-Gonzalez, Paola; Hinrichs, Rena; Jähne, Sebastian; Opazo, Felipe; Diederichsen, Ulf; Rizzoli, Silvio O.; Phan, Nhu T. N.
    Journal of Analytical Atomic Spectrometry 2019; 34(6) p.1083-1087
    Molecular imaging of targeted large biomolecules has been restricted in SIMS due to the limited number of probes containing SIMS-detectable isotopes. We introduce here new 19F-containing molecules that can be conjugated in a site-specific manner to nanobodies able to recognize fluorescent proteins (FPs) or mouse immunoglobulins (Igs). In this work, we demonstrate that it is possible to use the 19F-nanobodies to reveal the location of several cellular proteins previously tagged with FPs or Igs. This enables specific bio-imaging in SIMS for a vast repertoire of biomolecules, offering new opportunities to study specific structural and functional molecular interactions in biological specimens.
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  • Journal Article

    Orbital-Dependent Electronic Friction Significantly Affects the Description of Reactive Scattering of N 2 from Ru(0001) 

    Spiering, Paul; Shakouri, Khosrow; Behler, Jörg; Kroes, Geert-Jan; Meyer, Jörg
    The Journal of Physical Chemistry Letters 2019; 10(11) p.2957-2962
    Electron-hole pair (ehp) excitation is thought to substantially affect the dynamics of molecules on metal surfaces, but it is not clear whether this can be better addressed by orbital-dependent friction (ODF) or the local density friction approximation (LDFA). We investigate the effect of ehp excitation on the dissociative chemisorption of N2 on and its inelastic scattering from Ru(0001), which is the benchmark system of highly activated dissociation, with these two different models. ODF is in better agreement with the best experimental estimates for the reaction probabilities than LDFA, yields results for vibrational excitation in better agreement with experiment, but slightly overestimates the translational energy loss during scattering. N2 on Ru(0001) is thus the first system for which the ODF and LDFA approaches are shown to yield substantially different results for easily accessible experimental observables, including reaction probabilities.
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  • Journal Article

    Interconversion of Phosphinyl Radical and Phosphinidene Complexes by Proton Coupled Electron Transfer 

    Abbenseth, Josh; Delony, Daniel; Neben, Marc C.; Würtele, Christian; de Bruin, Bas; Schneider, Sven
    Angewandte Chemie International Edition 2019; 58(19) p.6338-6341
    The isolable complex [Os(PHMes*)H(PNP)] (Mes*=2,4,6-t Bu3 C6 H3 ; PNP=N{CHCHPt Bu2 }2 ) exhibits high phosphinyl radical character. This compound offers access to the phosphinidene complex [Os(PMes*)H(PNP)] by P-H proton coupled electron transfer (PCET). The P-H bond dissociation energy (BDE) was determined by isothermal titration calorimetry and supporting DFT computations. The phosphinidene product exhibits electrophilic reactivity as demonstrated by intramolecular C-H activation.
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  • Journal Article

    A bio-inspired imidazole-functionalised copper cage complex 

    Bete, Sarah C.; Würtele, Christian; Otte, Matthias
    Chemical Communications 2019; 55(30) p.4427-4430
    An imidazole-functionalised cage is synthesised that can coordinate to Cu(i). X-ray analysis reveals a T-shaped coordination of copper by the imidazole ligands reminiscent of the coordination geometry found in enzymatic active sites. This cage complex can catalyse the oxidation of benzylic alcohols to benzaldehydes utilizing oxygen as the terminal oxidant.
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  • Journal Article

    Inhibition of proteasome rescues a pathogenic variant of respiratory chain assembly factor COA7 

    Mohanraj, Karthik; Wasilewski, Michal; Benincá, Cristiane; Cysewski, Dominik; Poznanski, Jaroslaw; Sakowska, Paulina; Bugajska, Zaneta; Deckers, Markus; Dennerlein, Sven; Fernandez‐Vizarra, Erika; et al.
    Rehling, PeterDadlez, MichalZeviani, MassimoChacinska, Agnieszka
    EMBO Molecular Medicine 2019; 11(5): Art. e9561
    Nuclear and mitochondrial genome mutations lead to various mitochondrial diseases, many of which affect the mitochondrial respiratory chain. The proteome of the intermembrane space (IMS) of mitochondria consists of several important assembly factors that participate in the biogenesis of mitochondrial respiratory chain complexes. The present study comprehensively analyzed a recently identified IMS protein cytochrome c oxidase assembly factor 7 (COA7), or RESpiratory chain Assembly 1 (RESA1) factor that is associated with a rare form of mitochondrial leukoencephalopathy and complex IV deficiency. We found that COA7 requires the mitochondrial IMS import and assembly (MIA) pathway for efficient accumulation in the IMS. We also found that pathogenic mutant versions of COA7 are imported slower than the wild‐type protein, and mislocalized proteins are degraded in the cytosol by the proteasome. Interestingly, proteasome inhibition rescued both the mitochondrial localization of COA7 and complex IV activity in patient‐derived fibroblasts. We propose proteasome inhibition as a novel therapeutic approach for a broad range of mitochondrial pathologies associated with the decreased levels of mitochondrial proteins.
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  • Journal Article

    Accurate Probabilities for Highly Activated Reaction of Polyatomic Molecules on Surfaces Using a High-Dimensional Neural Network Potential: CHD 3 + Cu(111) 

    Gerrits, N.; Shakouri, Khosrow; Behler, Jörg; Kroes, Geert-Jan
    The Journal of Physical Chemistry Letters 2019; 10(8) p.1763-1768
    An accurate description of reactive scattering of molecules on metal surfaces often requires the modeling of energy transfer between the molecule and the surface phonons. Although ab initio molecular dynamics (AIMD) can describe this energy transfer, AIMD is at present untractable for reactions with reaction probabilities smaller than 1%. Here, we show that it is possible to use a neural network potential to describe a polyatomic molecule reacting on a mobile metal surface with considerably reduced computational effort compared to AIMD. The highly activated reaction of CHD3 on Cu(111) is used as a test case for this method. It is observed that the reaction probability is influenced considerably by dynamical effects such as the bobsled effect and surface recoil. A special dynamical effect for CHD3 + Cu(111) is that a higher vibrational efficacy is obtained for two quanta in the CH stretch mode than for a single quantum.
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  • Journal Article

    Photochemically Driven Reverse Water-Gas Shift at Ambient Conditions mediated by a Nickel Pincer Complex 

    Schneck, Felix; Schendzielorz, Florian; Hatami, Nareh; Finger, Markus; Würtele, Christian; Schneider, Sven
    Angewandte Chemie International Edition 2018; 57(44) p.14482-14487
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  • Journal Article

    A Ruthenium Hydrido Dinitrogen Core Conserved across Multielectron/Multiproton Changes to the Pincer Ligand Backbone 

    Bruch, Quinton J.; Lindley, Brian M.; Askevold, Bjorn; Schneider, Sven; Miller, Alexander J. M.
    Inorganic Chemistry 2018; 57(4) p.1964-1975
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  • Journal Article

    Four- and Five-Coordinate Osmium(IV) Nitrides and Imides: Circumventing the “Nitrido Wall” 

    Abbenseth, Josh; Bete, Sarah C.; Finger, Markus; Volkmann, Christian; Würtele, Christian; Schneider, Sven
    Organometallics 2017; 37(5) p.802-811
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  • Journal Article

    Magnetoelastic hybrid excitations in CeAuAl3 

    Čermák, Petr; Schneidewind, Astrid; Liu, Benqiong; Koza, Michael Marek; Franz, Christian; Schönmann, Rudolf; Sobolev, Oleg; Pfleiderer, Christian
    Proceedings of the National Academy of Sciences 2019; 116(14) p.6695-6700
    Nearly a century of research has established the Born–Oppenheimer approximation as a cornerstone of condensed-matter systems, stating that the motion of the atomic nuclei and electrons may be treated separately. Interactions beyond the Born–Oppenheimer approximation are at the heart of magneto-elastic functionalities and instabilities. We report comprehensive neutron spectroscopy and ab initio phonon calculations of the coupling between phonons, CEF-split localized 4f electron states, and conduction electrons in the paramagnetic regime of CeAuAl3, an archetypal Kondo lattice compound. We identify two distinct magneto-elastic hybrid excitations that form even though all coupling constants are small. First, we find a CEF–phonon bound state reminiscent of the vibronic bound state (VBS) observed in other materials. However, in contrast to an abundance of optical phonons, so far believed to be essential for a VBS, the VBS in CeAuAl3 arises from a comparatively low density of states of acoustic phonons. Second, we find a pronounced anticrossing of the CEF excitations with acoustic phonons at zero magnetic field not observed before. Remarkably, both magneto-elastic excitations are well developed despite considerable damping of the CEFs that arises dominantly by the conduction electrons. Taking together the weak coupling with the simultaneous existence of a distinct VBS and anticrossing in the same material in the presence of damping suggests strongly that similarly well-developed magneto-elastic hybrid excitations must be abundant in a wide range of materials. In turn, our study of the excitation spectra of CeAuAl3 identifies a tractable point of reference in the search for magneto-elastic functionalities and instabilities.
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  • Journal Article

    High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB 

    Bartsch, Annika; Llabrés, Salomé; Pein, Florian; Kattner, Christof; Schön, Markus; Diehn, Manuel; Tanabe, Mikio; Munk, Axel; Zachariae, Ulrich; Steinem, Claudia
    Scientific Reports 2019; 9(1): Art. 1264
    The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in porin channels.
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