No abstract

Aggregation without aggravation: A rapid and accurate estimation of the phase structure of amphiphilic molecules is made possible with a new computer simulation technique that excellently reproduces the aggregation behavior of such compounds. For dodecyldimethylamine oxide it is demonstrated how the micellar, hexagonal (see picture for isodensity profile), and lamella surfactant mesostructures can be calculated.

Interactions between metals and biomacromolecules including proteins, polysaccharides, and nucleic acids are important since they can be essential for a number of natural and industrial phenomena. These range from interactions of highly specific metal cofactors with particular proteins [1] to biosorption of heavy metals by polysaccharide hydrogels.[2]The unique features of DNA have been exploited in the development of novel materials, especially in the areas of medicine and nanotechnology. Classical research concerning antitumor drugs has focussed on the interactions of platinumor ruthenium-containing compounds with the major or minor grooves of polynucleotides. [3][4][5][6] There is a tremendous interest in the use of DNA in nanotechnology as a positioning template for the immobilization of metal nanoclusters with view to future applications in the construction of nanoelectronic devices. [7][8][9][10][11] Herein we report the interaction of Au 55 nanoclusters with the major grooves of B-DNA. The Au 55 clusters are degraded to Au 13 clusters by the transition of B-DNA into A-DNA in ultrahigh vacuum, and the resulting shrinkage of the major grooves. We have performed molecular-dynamics simulations and provided further information on the mechanism by which wires of Au 13 clusters form, and attempt to explain the interwire separation of 0.5 nm.

BackgroundAs an opportunistic human pathogen Pseudomonas aeruginosa is able to cause acute and chronic infections. The biofilm mode of life significantly contributes to the growth and persistence of P. aeruginosa during an infection process and mediates the pathogenicity of the bacterium. Within a biofilm mucoid strains of P. aeruginosa simultaneously produce and secrete several hydrolytic enzymes and the extracellular polysaccharide alginate. The focus of the current study was the interaction between extracellular lipase LipA and alginate, which may be physiologically relevant in biofilms of mucoid P. aeruginosa.ResultsFluorescence microscopy of mucoid P. aeruginosa biofilms were performed using fluorogenic lipase substrates. It showed a localization of the extracellular enzyme near the cells. A microtiter plate-based binding assay revealed that the polyanion alginate is able to bind LipA. A molecular modeling approach showed that this binding is structurally based on electrostatic interactions between negatively charged residues of alginate and positively charged amino acids of the protein localized opposite of the catalytic centre. Moreover, we showed that the presence of alginate protected the lipase activity by protection from heat inactivation and from degradation by the endogenous, extracellular protease elastase LasB. This effect was influenced by the chemical properties of the alginate molecules and was enhanced by the presence of O-acetyl groups in the alginate chain.ConclusionWe demonstrate that the extracellular lipase LipA from P. aeruginosa interacts with the polysaccharide alginate in the self-produced extracellular biofilm matrix of P. aeruginosa via electrostatic interactions suggesting a role of this interaction for enzyme immobilization and accumulation within biofilms. This represents a physiological advantage for the cells. Especially in the biofilm lifestyle, the enzyme is retained near the cell surface, with the catalytic centre exposed towards the substrate and is protected from denaturation and proteolytic degradation.

Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connected by harmonic springs to represent larger molecular entities in order to maintain a comparatively accurate representation of covalent bonding and molecular characteristics. For this study the MFD approach is extended to accomplish long-term simulations (up to the microsecond scale) of large molecular ensembles (representing millions of atoms) containing phospholipid membranes, peptides, and proteins. For peptides and proteins a generally applicable fragmentation scheme is introduced in combination with specific backbone forces that keep native spatial shapes with adequate levels of flexibility or rigidity. The new approach is demonstrated by MFD simulations of the formation and characteristics of phospholipid membranes and vesicles, vesicle-membrane fusion, the backbone force dependency of the overall structural flexibility of dumbbell-shaped Calmodulin, the stability of subunit-aggregation of tetrameric hemoglobin, and the collaborative interaction of Kalata B1 cyclotides with a phospholipid membrane. All findings are in reasonable agreement with experimental as well as alternative simulation results. Thus, the extended MFD approach may become a new tool for biomolecular system studies to allow for comparatively fast simulative investigations in combination with a comparatively high chemical granularity.