1. Slovar slovenskega knjižnega jezika 2024Aleksandra Bizjak Končar, Duša Divjak Race, Dejan Gabrovšek, Nataša Gliha Komac, Nataša Jakop, Janoš Ježovnik, Boris Kern, Simona Klemenčič, Domen Krvina, Nina Ledinek, Matej Meterc, Mija Michelizza, Tanja Mirtič, Andrej Perdih, Špela Petric, Marko Snoj, Andreja Žele, 2025, znanstveni terminološki slovar, enciklopedija ali tematski leksikon Objavljeno v DiRROS: 17.02.2026; Ogledov: 365; Prenosov: 169
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2. Lexical processing of morphologically complex Slovene words in a lexical decision task: the role of pseudowordsMatic Pavlič, Andrej Perdih, 2025, izvirni znanstveni članek Povzetek: This study investigates how the structure of pseudowords influences the lexical decision accuracy and response time in morphologically complex Slovene words. We tested three methods of constructing pseudowords: manual modification with preserved suffixes, manual modification with altered suffixes, and algorithmic generation with preserved suffixes, using the Wuggy application (Keuleers and Brysbaert 2010) adapted to Slovene. The pseudoword types did not differ significantly by accuracy, only by response time. However, these differences did not affect the accuracy rate or response time of existing Slovene words, suggesting that morphological complexity and manual/algorithmic construction of pseudowords are not relevant factors in lexical decision.
Ključne besede: pseudowords, lexical decision task, lexicography, Slovene, psycholinguistics
Objavljeno v DiRROS: 08.02.2026; Ogledov: 482; Prenosov: 152
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4. Water-based pharmacophore modeling in kinase inhibitor design : a case study on fyn and lyn protein kinasesMartin Ljubič, Marija Sollner Dolenc, Jure Borišek, Andrej Perdih, 2025, izvirni znanstveni članek Povzetek: Water-based pharmacophore modeling is an emerging approach in inhibitor design that leverages the dynamics of explicit water molecules within ligand-free, water-filled binding sites to derive 3D pharmacophores for virtual screening. In this study, we assess the potential of this strategy through a case study targeting the ATP binding sites of Fyn and Lyn protein kinases─members of the Src family that have been less explored in anticancer drug discovery compared to other family members. Molecular dynamics simulations of multiple kinase structures were used to generate and validate several water-derived pharmacophores, which were subsequently employed to screen chemically diverse libraries of compounds. Two active compounds were identified in biochemical assays: a flavonoid-like molecule with low-micromolar inhibitory activity and a weaker inhibitor from the library of nature-inspired synthetic compounds. Structural analysis via molecular docking and simulations revealed that key predicted interactions, particularly with the hinge region and the ATP binding pocket, were retained in the bound states of these hits. However, interactions with more flexible regions, such as the N-terminal lobe and activation loop, were less consistently captured. These findings outline both the strengths and challenges of using water-based pharmacophores: while effective at modeling conserved core interactions, they may miss peripheral contacts governed by protein flexibility. Incorporating ligand information where available may help address this challenge. Overall, water-based pharmacophore modeling presents a promising ligand-independent strategy for identifying novel chemotypes and exploring undercharged chemical and conformational space in kinases as well as other therapeutically relevant targets.
Ključne besede: drug discovery, inhibitors, ligands, peptides, proteins, pharmacophores
Objavljeno v DiRROS: 23.09.2025; Ogledov: 523; Prenosov: 299
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5. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: type IIA DNA topoisomerase, T-segment, C-gate, catalytic cycle, molecular dynamics
Objavljeno v DiRROS: 19.09.2025; Ogledov: 571; Prenosov: 314
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6. Nature-inspired substituted 3-(imidazol-2-yl) morpholines targeting human topoisomerase IIα : dynophore-derived discoveryBarbara Herlah, Matej Janežič, Iza Ogris, Simona Golič Grdadolnik, Katja Kološa, Sonja Žabkar, Bojana Žegura, Andrej Perdih, 2024, izvirni znanstveni članek Povzetek: The molecular nanomachine, human DNA topoisomerase IIα, plays a crucial role in replication, transcription, and recombination by catalyzing topological changes in the DNA, rendering it an optimal target for cancer chemotherapy. Current clinical topoisomerase II poisons often cause secondary tumors as side effects due to the accumulation of double-strand breaks in the DNA, spurring the development of catalytic inhibitors. Here, we used a dynamic pharmacophore approach to develop catalytic inhibitors targeting the ATP binding site of human DNA topoisomerase IIα. Our screening of a library of nature-inspired compounds led to the discovery of a class of 3-(imidazol-2-yl) morpholines as potent catalytic inhibitors that bind to the ATPase domain. Further experimental and computational studies identified hit compound 17, which exhibited selectivity against the human DNA topoisomerase IIα versus human protein kinases, cytotoxicity against several human cancer cells, and did not induce DNA double-strand breaks, making it distinct from clinical topoisomerase II poisons. This study integrates an innovative natural product-inspired chemistry and successful implementation of a molecular design strategy that incorporates a dynamic component of ligand-target molecular recognition, with comprehensive experimental characterization leading to hit compounds with potential impact on the development of more efficient chemotherapies.
Ključne besede: topoisomerase II, catalytic inhibitors, chemotherapy, DNA damage, cancer
Objavljeno v DiRROS: 03.06.2024; Ogledov: 1513; Prenosov: 893
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