# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.name
Structural and mechanistic insights into bacterial phospholipase A involved in membrane phospholipid degradation and virulence

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Cells steadily adapt their membrane glycerophospholipid (GPL) composition to changing environmental and developmental conditions. While the regulation of membrane homeostasis via GPL synthesis in bacteria has been studied in detail, the mechanisms underlying the controlled degradation of endogenous GPLs remain unknown. Thus far, the function of intracellular phospholipases A (PLAs) in GPL remodeling (Lands cycle) in bacteria is not clearly established. Here, we identified the first cytoplasmic membrane-bound phospholipase A1 (PlaF) from Pseudomonas aeruginosa, which might be involved in the Lands cycle. PlaF is an important virulence factor, as the P. aeruginosa ΔplaF mutant showed strongly attenuated virulence in Galleria mellonella and macrophages. We present a 2.0-Å-resolution crystal structure of PlaF, the first structure that reveals homodimerization of a single-pass transmembrane (TM) full-length protein. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. The dimerization site and the catalytic sites are linked by an intricate ligand-mediated interaction network, which might explain the product (fatty acid) feedback inhibition observed with the purified PlaF protein. We used molecular dynamics simulations and configurational free energy computations to suggest a model of PlaF activation through a coupled monomerization and tilting of the monomer in the membrane, which constrains the active site cavity into contact with the GPL substrates. Thus, these data indicate the importance of the PlaF mediated GPL remodeling pathway for virulence and could pave the way for the development of novel therapeutics targeting PlaF.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Structural and mechanistic insights into bacterial phospholipase A involved in membrane phospholipid degradation and virulence

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.name
Anomalous phylogenetic behavior of ribosomal proteins in metagenome assembled asgard archaea

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Supplement to a paper in GBE (title: Anomalous phylogenetic behavior of ribosomal proteins in metagenome assembled asgard archaea)

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This study was supported by the National Science Foundation of China (Nos. 91851210,
41530105), the Shenzhen Key Laboratory of Marine Archaea Geo-Omics, the Shenzhen
Science and Technology Innovation Commission (JCYJ20180305123458107), Southern
University of Science and Technology (No. ZDSYS20180208184349083), and the Southern
Marine Science and Engineering Guangdong Laboratory (Guangzhou) (No. K19313901).
This research was also funded by the Moore–Simons Project on the Origin of the Eukaryotic
Cell GBMF9743 to W.F.M. W.F.M. also would like to thank the ERC (666053), the VW
Foundation (93046 and 96742), and the DFG (Ma 1426/21-1) for funding.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.subject[].value
Metagenomics, binning, eukaryogenesis, phylogenetics, asgard archaea, candidate phylum radiation (CPR)

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Anomalous phylogenetic behavior of ribosomal proteins in metagenome assembled asgard archaea

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MD simulation data for: "Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
PlaF 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.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
MD simulation data for: "Molecular Mechanisms Underlying Medium-Chain Free Fatty Acid-regulated Activity of the Phospholipase PlaF from Pseudomonas aeruginosa"

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Simulation data for "Substrate access mechanism in a novel membrane-bound phospholipase A of Pseudomonas aeruginosa concordant with specificity and regioselectivity"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
PlaF is a cytoplasmic membrane-bound phospholipase A1 from Pseudomonas aeruginosa that alters the membrane glycerophospholipid (GPL) composition and fosters the virulence of this human pathogen. PlaF activity is regulated by a dimer-to-monomer transition followed by tilting of the monomer in the membrane. However, how substrates reach the active site and how the characteristics of the active site tunnels determine the activity, specificity, and regioselectivity of PlaF for natural GPL substrates has remained elusive. Here, we combined unbiased and biased all-atom molecular dynamics (MD) simulations and configurational free energy computations to identify access pathways of GPL substrates to the catalytic center of PlaF. Our results map out a distinct tunnel through which substrates access the catalytic center. PlaF variants with bulky tryptophan residues in this tunnel revealed decreased catalysis rates due to tunnel blockage. The MD simulations suggest that GPLs preferably enter the active site with the sn-1 acyl chain first, which agrees with the experimentally demonstrated PLA1 activity of PlaF. We propose that the acyl chain-length specificity of PlaF is determined by the structural features of the access tunnel, which results in favorable free energy of binding of medium-chain GPLs. The suggested egress route conveys fatty acid products to the dimerization interface and, thus, contributes to understanding the product feedback regulation of PlaF by fatty acid-triggered dimerization. These findings open up opportunities for developing potential PlaF inhibitors, which may act as antibiotics against P. aeruginosa.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Simulation data for "Substrate access mechanism in a novel membrane-bound phospholipase A of Pseudomonas aeruginosa concordant with specificity and regioselectivity"

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Molecular dynamics simulations data and analysis scripts used for Grx5 in the publication "Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
The files in this directory contain the molecular dynamics simulations data and analysis scripts for Grx5 used in the publication
"Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Molecular dynamics simulations data and analysis scripts used for Grx5 in the publication "Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

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Beteiligte Forschungsprojekte und deren FDM Anforderungen

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
An den drei Standorten gab es verschiedene Bedarfe der bestehenden (oder geplanten) Forschungsprojekte. In dieser Tabelle sind die wichtigsten Eckdaten der Projekte vermerkt.

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Beteiligte Forschungsprojekte und deren FDM Anforderungen

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Structural models of SFV Bet protein as SI for "Foamy Viruses, Bet, and APOBEC3 Restriction"

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Domain boundaries within the sequence of the SFV-chimpanzee Bet protein sequence were predicted with TopDomain. 
The two domains were modeled using the ROBETTA webserver. 
For each domain, ROBETTA generated five models. The best model was chosen based on the lowest Cα atom RMSD 
between the generated models and the corresponding ab initio modeled domain of PFV Bet. 
This consensus approach was also validated by TopScore in that domains with the lowest RMSD also have the 
lowest TopScore compared to the other four models. 
For the N-terminal domain, the overall TopScore is 0.47 and for the C-terminal one 0.45, indicating a moderate quality of the models. 
In the N-terminal domain, the helical part of the structure has low local TopScores, indicating good quality, 
but the N-terminal loops high local TopScores, indicating low quality. 
In the C-terminal domain, the β-strands have low local TopScores, indicating good quality, 
but helices and loops from residues 358–403 have high local TopScores, indicating low quality.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Structural models of SFV Bet protein as SI for "Foamy Viruses, Bet, and APOBEC3 Restriction"

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Table S4: Linearized laser induced fluroescence Stark spectrum of anisole at an electric field strength of 819:09Vcm􀀀1. The first column gives the relative frequeny in 1MHz increment, the second column the relative intensities.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Linearized laser induced fluroescence Stark spectrum of anisole at an electric
field strength of 819:09V/cm. The first column gives the relative frequeny in 1MHz
increment, the second column the relative intensities.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.subject[].value
Laser induced fluorescence Stark spectrum

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Table S4: Linearized laser induced fluroescence Stark spectrum of anisole at an electric field strength of 819:09Vcm􀀀1. The first column gives the relative frequeny in 1MHz increment, the second column the relative intensities.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Presentation slides for the training seminar about Open Science in Research Data Management of the FoDaKo-project: https://fodako.de

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MD simulation data for: "The cyclophilin A binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
All MD input structures, MD infiles, umbrella sampling files, and scripts that were used to analyze the umbrella sampling results are provided in this supporting repository.

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MD simulation data for: "The cyclophilin A binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1"

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Supporting Information for "Loading and Co-Solvent-Triggered Release of Okanin, a C4 Plant Key Enzyme Inhibitor, into/from Functional Microgels"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
The 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.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Supporting Information for "Loading and Co-Solvent-Triggered Release of Okanin, a C4 Plant Key Enzyme Inhibitor, into/from Functional Microgels"

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Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Hyperpolarization-activated and cyclic nucleotide (HCN) modulated channels are tetrameric cation channels. In each of the four subunits, the intracellular cyclic nucleotide-binding domain (CNBD) is coupled to the transmembrane domain via a helical structure, the C-linker. High-resolution channel structures suggest that the C-linker enables functionally relevant interactions with the opposite subunit, which might be critical for coupling the conformational changes in the CNBD to the channel pore. We combined mutagenesis, patch-clamp technique, confocal patch-clamp fluorometry, and molecular dynamics simulations to show that residue K464 of the C-linker is essential for stabilizing the closed state of the mHCN2 channel by forming interactions with the opposite subunit. MD simulations revealed that both cAMP and K464E induce a rotation of the intracellular domain relative to the channel pore, weakening the autoinhibitory effect of the unoccupied CL-CNBD region. The adopted poses are in excellent agreement with structural results.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Functional and structural characterization of interactions between opposite subunits in HCN pacemaker channels

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Ferredoxin reduction by hydrogen with iron functions as an evolutionary precursor of flavin-based electron bifurcation

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Ferredoxin reduction by hydrogen with iron functions as an evolutionary precursor of flavin-based electron bifurcation

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Molecular dynamics simulations data and analysis scripts used for Grx7 in the publication "Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
The files in this directory contain the molecular dynamics simulations data and analysis scripts for Grx7 used in the publication
"Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Molecular dynamics simulations data and analysis scripts used for Grx7 in the publication "Quantitative assessment of the determinant structural differences between redox-active and inactive glutaredoxins"

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Supporting Information for "Molecular modeling and simulations of DNA and RNA: DNAzyme as a model system"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Nowadays, the structural dynamics of DNA and RNA is accessible on an atomistic level on a micro- to millisecond time scale via molecular dynamics simulations. However, as DNA or RNA are highly charged molecules, performing such simulations is challenging as to the representation of intramolecular electrostatic interactions and those to solvent molecules and ions. This is particularly true for DNAzymes, where DNA and RNA backbones can come as close as 2.4 Å with their charged phosphate groups during the catalytic cycle. Here, we present tools to simulate the structural dynamics of a DNAzyme, with a focus on detailed instructions for the Amber suite of programs. Furthermore, we will show how to analyze metal ion binding within the DNAzyme.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Supporting Information for "Molecular modeling and simulations of DNA and RNA: DNAzyme as a model system"

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Supporting Information for "Molecular mechanisms underlying single nucleotide polymorphism-induced reactivity decrease in CYP2D6"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Cytochrome P450 2D6 (CYP2D6) is one of the most important enzymes involved in drug metabolism. Genetic polymorphism can influence drug metabolism by CYP2D6 such that a therapy is seriously affected by under- or overdosing of drugs. However, a general explanation at the atomistic level for poor activity is missing so far. Here we show for the 20 most common single nucleotide polymorphisms (SNPs) of CYP2D6 that poor metabolism is driven by four mechanisms. We found in extensive all-atom molecular dynamics simulations that the rigidity of the I-helix (central helix), distance between central phenylalanines (stabilizing bound substrate), availability of basic residues on the surface of CYP2D6 (binding of Cytochrome P450 reductase), and position of arginine 132 (electron transfer to heme) are essential for an extensive function of the enzyme. These results were applied to SNPs with unknown effects and potential SNPs that may lead to poor drug metabolism were identified. The revealed molecular mechanisms might be important for other drug-metabolizing Cytochrome P450 enzymes.

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.title[].value
Supporting Information for "Molecular mechanisms underlying single nucleotide polymorphism-induced reactivity decrease in CYP2D6"

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
Im Projekt FoDaKo wurden verschiedene Softwarelösungen verglichen. Hier finden sich die Bewertungskriterien für Middleware Softwarelösungen in Zusammenhang mit dem Auswählen einer Repositoriumlösung für die drei Standorte. Folgende mögliche Softwarelösungen sollten bewertet werden: CKAN, DSpace und Invenio

# _embedded.searchResult._embedded.objects[]._embedded.indexableObject.metadata.dc.description.abstract[].value
This is the TopDomain dataset as described in: "TopDomain: Exhaustive Protein Domain
Boundary Meta-Prediction Combining Multi-Source Information and Deep Learning" by Daniel Mulnaes, Pegah Golchin, Filip Koenig, and Holger Gohlke. This dataset contains two folder: training_set : Contains the fasta files of the TopDomain training set; test_set: Contains the fasta files of the TopDomain test set. Each fasta file has a header with three fields, in the following format: ">system_name|domain_type|boundary_list". Where: 
system_name   contains the PDB ID and chain ID of the target protein; domain_type contains target type, either single-domain or multi-domain; boundary_list contains a list of residues annotated as domain boundaries separated by spaces, this field is empty for single-domain proteins as they have no domain boundaries. 
The sequence is the fasta-sequence of the protein, each line contains at most 100 residues of the protein sequence. No protein in the test set shares more than 20% sequence identity to any protein in the training set.