SQM2.20: Semiempirical quantum-mechanical scoring function yields DFT-quality protein–ligand binding affinity predictions in minutes

Autor: Adam Pecina, Jindřich Fanfrlík, Martin Lepšík, Jan Řezáč

Publikováno v: Nature Communications, Vol 15, Iss 1, Pp 1-10 (2024)

Abstract Accurate estimation of protein–ligand binding affinity is the cornerstone of computer-aided drug design. We present a universal physics-based scoring function, named SQM2.20, addressing key terms of binding free energy using semiempirical

Externí odkaz: https://doaj.org/article/517c9f3900db4a11a34a83b1a51e58d9

Highly potent inhibitors of cathepsin K with a differently positioned cyanohydrazide warhead: structural analysis of binding mode to mature and zymogen-like enzymes

Autor: Jakub Benýšek, Michal Buša, Petra Rubešová, Jindřich Fanfrlík, Martin Lepšík, Jiří Brynda, Zuzana Matoušková, Ulrike Bartz, Martin Horn, Michael Gütschow, Michael Mareš

Publikováno v: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 37, Iss 1, Pp 515-526 (2022)

Cathepsin K (CatK) is a target for the treatment of osteoporosis, arthritis, and bone metastasis. Peptidomimetics with a cyanohydrazide warhead represent a new class of highly potent CatK inhibitors; however, their binding mechanism is unknown. We in

Externí odkaz: https://doaj.org/article/c51df7b09c7a427fa4eefb8b01b73746

Structural characterization of CAS SH3 domain selectivity and regulation reveals new CAS interaction partners

Autor: Jakub Gemperle, Rozálie Hexnerová, Martin Lepšík, Petr Tesina, Michal Dibus, Marian Novotný, Jan Brábek, Václav Veverka, Daniel Rosel

Publikováno v: Scientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)

Abstract CAS is a docking protein downstream of the proto-oncogene Src with a role in invasion and metastasis of cancer cells. The CAS SH3 domain is indispensable for CAS-mediated signaling, but structural aspects of CAS SH3 ligand binding and regula

Externí odkaz: https://doaj.org/article/9f3efa9a9d654d38ab0c7c109782bb44

The Role of Cysteine Residues in Catalysis of Phosphoenolpyruvate Carboxykinase from Mycobacterium tuberculosis.

Autor: Iva Machová, Martin Hubálek, Martin Lepšík, Lucie Bednárová, Markéta Pazderková, Vladimír Kopecký, Jan Snášel, Jiří Dostál, Iva Pichová

Publikováno v: PLoS ONE, Vol 12, Iss 1, p e0170373 (2017)

Mycobacterium tuberculosis (MTb), the causative agent of tuberculosis, can persist in macrophages for decades, maintaining its basic metabolic activities. Phosphoenolpyruvate carboxykinase (Pck; EC 4.1.1.32) is a key player in central carbon metaboli

Externí odkaz: https://doaj.org/article/8b39c3a24d804c8aa7cdc914dd6e067a

A rapid synthesis of low-nanomolar divalent LecA inhibitors in four linear steps from d-galactose pentaacetate

Autor: Eva Zahorska, Alexander Titz, Sakonwan Kuhaudomlarp, Martin Lepšík, Saverio Minervini, Anne Imberty, Anna K. H. Hirsch, Sultaan Yousaf, Thorsten Kinsinger

Publikováno v: Chemical Communications
Chemical Communications, Royal Society of Chemistry, 2020, ⟨10.1039/D0CC03490H⟩
Chemical communications (Cambridge, England)
England

Chronic infections with Pseudomonas aeruginosa are associated with the formation of bacterial biofilms. The tetrameric P. aeruginosa lectin LecA is a virulence factor and an anti-biofilm drug target. Increasing the overall binding affinity by multiva

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::92be499fef1c3f0c16c622bb40e4c696