The Faculty of Mathematics and Natural Sciences
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The Faculty of Mathematics and Natural Sciences (MNF) employs more than 800 Scientists in seven departments: Biology, Chemistry, Computer Sciences, Mathematics, Pharmacy, Physics and Psychology. Among the wide-ranging research areas covered by the faculty, several cooperative programmes put specific emphasis on Life Sciences and Physics.
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Browsing The Faculty of Mathematics and Natural Sciences by Subject "Amber"
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Item MD simulation data for: "Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa"(N/A, 2023-11) Gentile, Rocco; Schott-Verdugo, Stephan; Gohlke, HolgerPlaF is a membrane-bound phospholipase A1 from P. aeruginosa that is involved in remodeling membrane glycerophospholipids (GPLs) and modulation of virulence-associated signaling and metabolic pathways. Previously, we identified the role of medium-chain free fatty acids (FFA) in inhibiting PlaF activity and promoting homodimerization, yet the underlying molecular mechanism remained elusive. Here, we used unbiased and biased molecular dynamics simulations and free energy computations to assess how PlaF interacts with FFAs localized in the water milieu surrounding the bilayer or within the bilayer, and how these interactions regulate PlaF activity. Medium-chain FFAs localized in the upper bilayer leaflet can stabilize inactive dimeric PlaF, likely through interactions with charged surface residues as experimentally validated. Potential of mean force (PMF) computations indicate that membrane-bound FFAs may facilitate the activation of monomeric PlaF by lowering the activation barrier of changing into a tilted, active configuration. We estimated that the coupled equilibria of PlaF monomerization-dimerization and tilting at the physiological concentration of PlaF lead to the majority of PlaF forming inactive dimers when in a cell membrane loaded with decanoic acid (C10). This is in agreement with a suggested in vivo product feedback loop and GC-MS profiling results indicating that PlaF catalyzes the release of C10 from P. aeruginosa membranes. Additionally, we found that C10 in the water milieu can access the catalytic site of active monomeric PlaF, contributing to the competitive component of C10-mediated PlaF inhibition. Our study provides mechanistic insights into how medium-chain FFA may regulate the activity of PlaF, a potential bacterial drug target.Item Supporting Information for "Loading and Co-Solvent-Triggered Release of Okanin, a C4 Plant Key Enzyme Inhibitor, into/from Functional Microgels"(N/A, 2023-01) Dittrich, Jonas; Gohlke, HolgerThe constantly growing world population leads to increasing demands for food, which challenges modern agriculture manifold. Pests, such as weeds, require the application of agrochemicals to increase crop yield. Due to the environmental impact of these potentially hazardous chemicals, the demand for more efficient formulations is increasing. Promising formulations consist of easily adaptable carriers from which controllable stimuli release the agrochemicals. Here, we investigated poly(N vinylcaprolactam) (pVCL)-based microgels as a potential carrier for okanin, an inhibitor of the C4 plant key enzyme phosphoenolpyruvate carboxylase, by combining experiments, molecular simulations, and free energy computations. Dynamic light scattering, scanning transmission electron and atomic force microscopy revealed that pVCL microgels collapse and rigidify upon the loading of okanin. The simulations identified loosely adsorbed okanin and tightly bound okanin mediating inter-chain crosslinks. With increasing okanin concentration, stacking interactions of okanin occur with adsorbed and bound okanin. These findings can explain the experimentally observed collapse and the rigidification of the microgels. Based on the atomistic insights, two poly(N vinylcaprolactam co glycidyl methacrylate) microgels were synthesized, for which a doubled loading capacity of okanin was found. Finally, we investigated the triggered release of okanin using the addition of green solvents as a stimulus. This work establishes a basis for the further optimization of pVCL-based microgels as a carrier for the delivery of polyphenolic agrochemicals.