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2. Asymmetric T-segment binding and gate dynamics govern the final stages of the type IIA topoisomerase catalytic cycleKristina Stevanović, Barbara Herlah, Matic Pavlin, Andrej Perdih, 2025, original scientific article Abstract: Type IIA DNA topoisomerases are molecular nanomachines that alter DNA topology during essential cellular processes. The final steps of their catalytic cycle, after translocation of the transported (T-) segment into the C- gate, are still not fully understood. Here, we performed all-atom molecular dynamics simulations of several conformational states of Saccharomyces cerevisiae topoisomerase IIA, each with a T-segment inserted into the C- gate. Bound ATP and ADP nucleotides allosterically modulated the N-gate dynamics, likely stabilizing the dimer and preventing premature dissociation. The T-segment was asymmetrically bound and stabilized within the C- gate by positively charged residues, and this gate remained structurally rigid, highlighting its role as a retention site. The positioning of the T-segment in the C-gate allosterically influenced the G-segment to a straighter geometry that favors religation and release. Our simulations support coordinated release of DNA segments and point to a potentially important role for dynamic communication between the gates in the mechanism. These results provide new insights into the late stages of the catalytic cycle and highlight the intertwined roles of nucleotide binding, DNA topology and coupled protein domain dynamics in regulating this important enzyme.
Keywords: type IIA DNA topoisomerase, T-segment, C-gate, catalytic cycle, molecular dynamics
Published in DiRROS: 19.09.2025; Views: 430; Downloads: 206
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3. In silico determination of novel SARS-CoV-2 envelope protein ion channel inhibitorsNina Kobe, Lennart Dreisewerd, Matic Pavlin, Polona Kogovšek, Črtomir Podlipnik, Uroš Grošelj, Miha Lukšič, 2025, original scientific article Abstract: The SARS-CoV-2 envelope protein (2-EPRO), a viroporin crucial for viral pathogenesis, is a promising target for antiviral drug development as it is highly conserved and functionally important. Although it is a promising therapeutic target for the treatment of COVID-19, it has often been overlooked in previous studies. In this study, a high-throughput virtual screening of nearly one billion compounds was performed, followed by rigorous filtering and re-docking. Eight best-scoring and chemically versatile lead candidates were identified. In molecular dynamics simulations, three of these ligands showed stable protein-ligand complexes occupying the 2-EPRO channel pore. Among these, ZINC001799167680 (L3) and ZINC001081252239 (L2) exhibited the strongest binding a˙inity, with key interactions at residues ASN15, THR11 and GLU8 identified by Molecular Mechanics Poisson-Boltzmann Surface Area analysis. All ligands were compared with the known inhibitor rimantadine and showed stronger binding to the protein. These in silico results highlight the potential of focusing on the 2-EPRO ion channel in the development of novel COVID-19 therapeutics and pave the way for further in vitro and in vivo studies.
Keywords: SARS-CoV-2 envelope protein, viroporin, ion channel, channel blockers, molecular dynamics simulations, free energy calculations, drug discovery
Published in DiRROS: 05.09.2025; Views: 439; Downloads: 191
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4. Merging heterogeneous graphitic carbon nitride photocatalysis with cobaloxime catalysis in uphill dehydrogenative synthesis of anilinesSonia Zoltowska, Stefano Mazzanti, Sara Stolfi, Jingsan Xu, Matej Huš, Ana Oberlintner, Matic Pavlin, Paolo Ghigna, Blaž Likozar, Piero Torelli, 2025, original scientific article Published in DiRROS: 20.08.2025; Views: 455; Downloads: 231
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6. Disrupting Cu trafficking as a potential therapy for cancerZena Qasem, Matic Pavlin, Ida Ritacco, Matan Y. Avivi, Shelly Meron, Melanie Hirsch, Yulia Shenberger, Lada Gevorkyan-Airapetov, Alessandra Magistrato, Sharon Ruthstein, 2022, original scientific article Published in DiRROS: 03.01.2023; Views: 1721; Downloads: 798
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