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 Author "Becker, Daniel"
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Item MD simulation data for: "The cyclophilin A binding loop of the capsid regulates the human TRIM5α sensitivity of nonpandemic HIV-1"(N/A, 2023-11) Becker, Daniel; Münk, Carsten; Gohlke, HolgerAll 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.Item Structural models of SFV Bet protein as SI for "Foamy Viruses, Bet, and APOBEC3 Restriction"(N/A, 2021-03-18) Vasudevan, Ananda; Becker, Daniel; Luedde, Tom; Gohlke, Holger; Muenk, CarstenDomain 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.Item Supporting Information for "F/G-Region Rigidity is Inversely Correlated to Substrate Promiscuity of Human CYP Isoforms Involved in Metabolism"(N/A, 2021-07-13) Becker, Daniel; Bharatam, Prasad; Gohlke, HolgerOf 57 human Cytochrome P450 (CYP) enzymes, twelve metabolize 90% of xenobiotics. To our knowledge, no study has addressed the relation between enzyme dynamics and substrate promiscuity for more than three CYPs. Here, we show by constraint dilution simulations with the Constraint Network Analysis for the twelve isoforms that structural rigidity of the F/G-region is significantly inversely correlated to the enzymes’ substrate promiscuity. This highlights the functional importance of structural dynamics of the substrate tunnel.Item Supporting Information for "Molecular mechanisms underlying single nucleotide polymorphism-induced reactivity decrease in CYP2D6"(N/A, 2024-02) Becker, Daniel; Gohlke, HolgerCytochrome 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.