08 Fakultät Mathematik und Physik

Permanent URI for this collectionhttps://elib.uni-stuttgart.de/handle/11682/9

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Institute: search.filters.UBSInstitut.Institut für ComputerphysikSubject: search.filters.subject.570

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Now showing 1 - 4 of 4
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    Solubilization of inclusion bodies : insights from explainable machine learning approaches
    (2023) Walther, Cornelia; Martinetz, Michael C.; Friedrich, Anja; Tscheließnig, Anne-Luise; Voigtmann, Martin; Jung, Alexander; Brocard, Cécile; Bluhmki, Erich; Smiatek, Jens
    We present explainable machine learning approaches for gaining deeper insights into the solubilization processes of inclusion bodies. The machine learning model with the highest prediction accuracy for the protein yield is further evaluated with regard to Shapley additive explanation (SHAP) values in terms of feature importance studies. Our results highlight an inverse fractional relationship between the protein yield and total protein concentration. Further correlations can also be observed for the dominant influences of the urea concentration and the underlying pH values. All findings are used to develop an analytical expression that is in reasonable agreement with experimental data. The resulting master curve highlights the benefits of explainable machine learning approaches for the detailed understanding of certain biopharmaceutical manufacturing steps.
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    Molecular dynamics simulations for the study of interaction between non-canonical DNA structures and biochemically relevant co-solutes
    (2023) Oprzeska-Zingrebe, Ewa Anna; Smiatek, Jens (Priv.-Doz. Dr.)
    Non-canonical nucleic acid structures, such as DNA G-quadruplexes and i-Motifs, have been proved to play an important role in key biological processes, including gene expression, replication, regulation or telomere maintenance. The presence of G-quadruplexes in promoter regions of certain oncogenes turn them into a potential target for cancer therapies. Besides their biological implications, non-canonical DNA structures are present in genomes of various organisms, who adopt certain levels of co-solutes to protect their internal structures against the harsh environment. This study presents the research on the selected non-canonical DNA structures of particular biological relevance: G-quadruplex with only two tetrads, small DNA hairpin and ssDNA strand as well as canonical double helix. The atomistic molecular dynamics (MD) simulations have been applied to elucidate the structural, configuration and solvation properties of the analyzed structures in the presence of assorted co-solutes, composing the native cellular environment in nature: urea, ectoine and trimethylamine-N-oxide (TMAO). With the application of molecular theory of solutions, one determines and exemplifies the thermodynamic properties of investigated structures in various environments close to the physiological conditions present in living cells. This study uncovers the versatile nature of DNA interaction with diverse co-solutes and water, as well as the cross-interactions between the inorganic components of the biomolecular solution. The cellular mechanisms of DNA structural stabilization and destabilization are hereby described in terms of preferential binding and preferential exclusion, with particular emphasis on the properties of solvent structure within individual solvation shells. In this regards, this work presents a comprehensive study on the intracellular interactions involving nucleic acids, thus shedding light into their microscopic properties and opening the path for further biomedical research.
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    Influence of bacterial swimming and hydrodynamics on attachment of phages
    (2024) Lohrmann, Christoph; Holm, Christian; Datta, Sujit S.
    Bacteriophages (“phages”) are viruses that infect bacteria. Since they do not actively self-propel, phages rely on thermal diffusion to find target cells - but can also be advected by fluid flows, such as those generated by motile bacteria themselves in bulk fluids. How does the flow field generated by a swimming bacterium influence how it encounters phages? Here, we address this question using coupled molecular dynamics and lattice Boltzmann simulations of flagellated bacteria swimming through a bulk fluid containing uniformly-dispersed phages. We find that while swimming increases the rate at which phages attach to both the cell body and flagellar propeller, hydrodynamic interactions strongly suppress this increase at the cell body, but conversely enhance this increase at the flagellar bundle. Our results highlight the pivotal influence of hydrodynamics on the interactions between bacteria and phages, as well as other diffusible species, in microbial environments.
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    Functionalized nanogap for DNA read‐out : nucleotide rotation and current‐voltage curves
    (2020) Maier, Frank C.; Fyta, Maria
    Functionalized nanogaps embedded in nanopores show a strong potential for enhancing the detection of biomolecules, their length, type, and sequence. This detection is strongly dependent on the features of the target biomolecules, as well as the characteristics of the sensing device. In this work, through quantum‐mechanical calculations, we elaborate on representative such aspects for the specific case of DNA detection and read‐out. These aspects include the influence of single DNA nucleotide rotation within the nanogap and the current‐voltage (I‐V) characteristics of the nanogap. The results unveil a distinct variation in the electronic current across the functionalized device for the four natural DNA nucleotides with the applied voltage. These also underline the asymmetric response of the rotating nucleotides on this applied voltage and the respective variation in the rectification ratio of the device. The electronic tunneling current across the nanogap can be further enhanced through the proper choice of an applied bias voltage. We were able to correlate the enhancement of this current to the nucleotide rotation dynamics and a shift of the electronic transmission peaks towards the Fermi level. This nucleotide specific shift further reveals the sensitivity of the device in reading‐out the identity of the DNA nucleotides for all different configurations in the nanogap. We underline the important information that can be obtained from both the I‐V curves and the rectification characteristics of the nanogap device in view of accurately reading‐out the DNA information. We show that tuning the applied bias can enhance this detection and discuss the implications in view of novel functionalized nanopore sequencers.