Role of anisotropy for protein-protein encounter

Protein-protein interactions comprise both transport and reaction steps. During the transport step, anisotropy of proteins and their complexes is important both for hydrodynamic diffusion and accessibility of the binding site. Using a Brownian dynamics approach and extensive computer simulations, we quantify the effect of anisotropy on the encounter rate of ellipsoidal particles covered with spherical encounter patches. We show that the encounter rate $k$ depends on the aspect ratios $\xi$ mainly through steric effects, while anisotropic diffusion has only a little effect. Calculating analytically the crossover times from anisotropic to isotropic diffusion in three dimensions, we find that they are much smaller than typical protein encounter times, in agreement with our numerical results.Comment: 4 pages, Revtex with 3 figures, to appear as a Rapid Communication in Physical Review

Dynamics of protein-protein encounter: a Langevin equation approach with reaction patches

We study the formation of protein-protein encounter complexes with a Langevin equation approach that considers direct, steric and thermal forces. As three model systems with distinctly different properties we consider the pairs barnase:barstar, cytochrome c:cytochrome c peroxidase and p53:MDM2. In each case, proteins are modeled either as spherical particles, as dipolar spheres or as collection of several small beads with one dipole. Spherical reaction patches are placed on the model proteins according to the known experimental structures of the protein complexes. In the computer simulations, concentration is varied by changing box size. Encounter is defined as overlap of the reaction patches and the corresponding first passage times are recorded together with the number of unsuccessful contacts before encounter. We find that encounter frequency scales linearly with protein concentration, thus proving that our microscopic model results in a well-defined macroscopic encounter rate. The number of unsuccessful contacts before encounter decreases with increasing encounter rate and ranges from 20-9000. For all three models, encounter rates are obtained within one order of magnitude of the experimentally measured association rates. Electrostatic steering enhances association up to 50-fold. If diffusional encounter is dominant (p53:MDM2) or similarly important as electrostatic steering (barnase:barstar), then encounter rate decreases with decreasing patch radius. More detailed modeling of protein shapes decreases encounter rates by 5-95 percent. Our study shows how generic principles of protein-protein association are modulated by molecular features of the systems under consideration. Moreover it allows us to assess different coarse-graining strategies for the future modelling of the dynamics of large protein complexes

Vorwort. Jubiläen und Zwischenbilanzen – Mit Lob und Kritik schon wieder zum Aufbruch?

Anlässlich des 50. Bandes der Buchreihe der Gesellschaft für Medien in der Wissenschaft ziehen die Autoren im Vorwort des Sammelwerkes zur Geschichte und zum Thema des E-Learning Zwischenbilanz. Unter den Schwerpunkten E-Learning-Förderung (1.), Didaktik (2.), Sicht der Anwender (3.), Institution Hochschule (4.) und Visionen fassen sie die Inhalte der einzelnen Beiträge des Buches zusammen. (DIPF/ ssch.

Galerkin-type coupled Boundary Element Method for Time domain simulations on Discontinuous surfaces

In the context of this abstract, we present the 2D and linearized Galerkin-type coupled BEM (cBEM) that solves for the mixed boundary value problem (BVP) containing the discontinuous free surface and body surface. The incorporation of the high order spectral (HOS) method, introduced by West et al. (1987) and Dommermuth & Yue (1987), allows the monolithic coupling of wave and body dynamics. In the presented application, small amplitude motions of a surface piercing body around its equilibrium position are considered. High-order basis functions are used to approximate the solution function space composed of the velocity potential $\phi$ and its normal derivative $\frac{\partial \phi}{\partial n}$, and the geometry of the body. We discuss the verification of cBEM with an analytic reference solution and demonstrate the validity of the solver for hydrodynamic problems with experimental and numerical data

Superconformal M2-branes and generalized Jordan triple systems

Three-dimensional conformal theories with six supersymmetries and SU(4) R-symmetry describing stacks of M2-branes are here proposed to be related to generalized Jordan triple systems. Writing the four-index structure constants in an appropriate form, the Chern-Simons part of the action immediately suggests a connection to such triple systems. In contrast to the previously considered three-algebras, the additional structure of a generalized Jordan triple system is associated to a graded Lie algebra, which corresponds to an extension of the gauge group. In this note we show that the whole theory with six manifest supersymmetries can be naturally expressed in terms of such a graded Lie algebra. Also the BLG theory with eight supersymmetries is included as a special case.Comment: 15 pages, v2 and v3: minor corrections and clarifications, references added, v2: section 4 extended, v3: published versio

Probing the crossover in CO desorption from single crystal to nanoparticulate Ru model catalysts

cited By 10International audienceUsing model catalysts, we demonstrate that CO desorption from Ru surfaces can be switched from that typical of single crystal surfaces to one more characteristic of supported nanoparticles. First, the CO desorption behaviour from Ru nanoparticles supported on highly oriented pyrolytic graphite was studied. Both mass-selected and thermally evaporated nanoparticles were deposited. TPD spectra from the mass-selected nanoparticles exhibit a desorption peak located around 410 K with a broad shoulder extending from around 480 K to 600 K, while spectra obtained from thermally evaporated nanoparticles exhibit a single broad feature from ∼350 K to ∼450 K. A room temperature deposited 50 Å thick Ru film displays a characteristic nanoparticle-like spectrum with a broad desorption feature at ∼420 K and a shoulder extending from ∼450 K to ∼600 K. Subsequent annealing of this film at 900 K produced a polycrystalline morphology of flat Ru(001) terraces separated by monatomic steps. The CO desorption spectrum from this surface resembles that obtained on single crystal Ru(001) with two large desorption features located at 390 K and 450 K due to molecular desorption from terrace sites, and a much smaller peak at ∼530 K due to desorption of dissociatively adsorbed CO at step sites. In a second experiment, ion sputtering was used to create surface defects on a Ru(0 1 54) single crystal surface. A gradual shift away from the desorption spectrum typical of a Ru(001) surface towards one resembling desorption from supported Ru nanoparticles was observed with increasing sputter time. © 2011 the Owner Societies

HLA-DP on Epithelial Cells Enables Tissue Damage by NKp44+ Natural Killer Cells in Ulcerative Colitis

Background & aims: Ulcerative colitis (UC) is characterized by severe inflammation and destruction of the intestinal epithelium, and is associated with specific risk single nucleotide polymorphisms in HLA class II. Given the recently discovered interactions between subsets of HLA-DP molecules and the activating natural killer (NK) cell receptor NKp44, genetic associations of UC and HLA-DP haplotypes and their functional implications were investigated.Methods: HLA-DP haplotype and UC risk association analyses were performed (UC: n = 13,927; control: n = 26,764). Expression levels of HLA-DP on intestinal epithelial cells (IECs) in individuals with and without UC were quantified. Human intestinal 3-dimensional (3D) organoid cocultures with human NK cells were used to determine functional consequences of interactions between HLA-DP and NKp44.Results: These studies identified HLA-DPA1∗01:03-DPB1∗04:01 (HLA-DP401) as a risk haplotype and HLA-DPA1∗01:03-DPB1∗03:01 (HLA-DP301) as a protective haplotype for UC in European populations. HLA-DP expression was significantly higher on IECs of individuals with UC compared with controls. IECs in human intestinal 3D organoids derived from HLA-DP401pos individuals showed significantly stronger binding of NKp44 compared with HLA-DP301pos IECs. HLA-DP401pos IECs in organoids triggered increased degranulation and tumor necrosis factor production by NKp44+ NK cells in cocultures, resulting in enhanced epithelial cell death compared with HLA-DP301pos organoids. Blocking of HLA-DP401-NKp44 interactions (anti-NKp44) abrogated NK cell activity in cocultures.Conclusions: We identified an UC risk HLA-DP haplotype that engages NKp44 and activates NKp44+ NK cells, mediating damage to intestinal epithelial cells in an HLA-DP haplotype-dependent manner. The molecular interaction between NKp44 and HLA-DP401 in UC can be targeted by therapeutic interventions to reduce NKp44+ NK cell-mediated destruction of the intestinal epithelium in UC

Three-algebras, triple systems and 3-graded Lie superalgebras

The three-algebras used by Bagger and Lambert in N=6 theories of ABJM type are in one-to-one correspondence with a certain type of Lie superalgebras. We show that the description of three-algebras as generalized Jordan triple systems naturally leads to this correspondence. Furthermore, we show that simple three-algebras correspond to simple Lie superalgebras, and vice versa. This gives a classification of simple three-algebras from the well known classification of simple Lie superalgebras.Comment: 21 pages. v2: published versio