TY - JOUR AU - Szél, Viktor AU - Zsidó, Balázs Zoltán AU - Jeszenői, Norbert AU - Hetényi, Csaba TI - Target-ligand binding affinity from single point enthalpy calculation and elemental composition JF - PHYSICAL CHEMISTRY CHEMICAL PHYSICS J2 - PHYS CHEM CHEM PHYS VL - 25 PY - 2023 IS - 46 SP - 31714 EP - 31725 PG - 12 SN - 1463-9076 DO - 10.1039/d3cp04483a UR - https://m2.mtmt.hu/api/publication/34377793 ID - 34377793 N1 - Export Date: 19 February 2024 CODEN: PPCPF Correspondence Address: Hetényi, C.; Pharmacoinformatics Unit, Szigeti út 12, Hungary; email: hetenyi.csaba@pte.hu AB - Reliable target-ligand binding thermodynamics data are essential for successful drug design and molecular engineering projects. Besides experimental methods, a number of theoretical approaches have been introduced for the generation of binding thermodynamics data. However, available approaches often neglect electronic effects or explicit water molecules influencing target-ligand interactions. To handle electronic effects within a reasonable time frame, we introduce a fast calculator QMH-L using a single target-ligand complex structure pre-optimized at the molecular mechanics level. QMH-L is composed of the semi-empirical quantum mechanics calculation of binding enthalpy with predicted explicit water molecules at the complex interface, and a simple descriptor based on the elemental composition of the ligand. QMH-L estimates the target-ligand binding free energy with a root mean square error (RMSE) of 0.94 kcal mol-1. The calculations also provide binding enthalpy values and they were compared with experimental binding thermodynamics data collected from the most reliable isothermal titration calorimetry studies of systems including various protein targets and challenging, large peptide ligands with a molecular weight of up to 2-3 thousand. The single point enthalpy calculations of QMH-L require modest computational resources and are based on short runs with open source and/or free software like Gromacs, Mopac, MobyWat, and Fragmenter. QMH-L can be applied for fast, automated scoring of drug candidates during a virtual screen, enthalpic engineering of new ligands or thermodynamic explanation of complex interactions. LA - English DB - MTMT ER - TY - GEN AU - Hetényi, Csaba AU - Zsidó, Balázs Zoltán AU - Börzsei, Rita AU - Szél, Viktor TI - The Role of Water in Material Design: Improved Models for Molecular and Quantum Mechanical Simulations PY - 2023 UR - https://m2.mtmt.hu/api/publication/34192396 ID - 34192396 LA - English DB - MTMT ER - TY - GEN AU - Hetényi, Csaba AU - Szél, Viktor AU - Zsidó, Balázs Zoltán AU - Börzsei, Rita TI - Optimization of Drug-Target Interactions Using Fast Pharmacoinformatics Protocols PY - 2023 UR - https://m2.mtmt.hu/api/publication/34192188 ID - 34192188 LA - English DB - MTMT ER - TY - JOUR AU - Zsidó, Balázs Zoltán AU - Bayarsaikhan, Bayartsetseg AU - Börzsei, Rita AU - Hetényi, Csaba TI - Construction of Histone-Protein Complex Structures by Peptide Growing JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 18 PG - 17 SN - 1661-6596 DO - 10.3390/ijms241813831 UR - https://m2.mtmt.hu/api/publication/34167335 ID - 34167335 N1 - * Megosztott szerzőség AB - The structures of histone complexes are master keys to epigenetics. Linear histone peptide tails often bind to shallow pockets of reader proteins via weak interactions, rendering their structure determination challenging. In the present study, a new protocol, PepGrow, is introduced. PepGrow uses docked histone fragments as seeds and grows the full peptide tails in the reader-binding pocket, producing atomic-resolution structures of histone-reader complexes. PepGrow is able to handle the flexibility of histone peptides, and it is demonstrated to be more efficient than linking pre-docked peptide fragments. The new protocol combines the advantages of popular program packages and allows fast generation of solution structures. AutoDock, a force-field-based program, is used to supply the docked peptide fragments used as structural seeds, and the building algorithm of Modeller is adopted and tested as a peptide growing engine. The performance of PepGrow is compared to ten other docking methods, and it is concluded that in situ growing of a ligand from a seed is a viable strategy for the production of complex structures of histone peptides at atomic resolution. LA - English DB - MTMT ER - TY - JOUR AU - Balázs, Orsolya AU - Dombi, Ágnes AU - Zsidó, Balázs Zoltán AU - Hetényi, Csaba AU - Valentová, Kateřina AU - Vida, Róbert György AU - Poór, Miklós TI - Inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by luteolin, naringenin, myricetin, ampelopsin and their conjugated metabolites. JF - BIOMEDICINE & PHARMACOTHERAPY J2 - BIOMED PHARMACOTHER VL - 167 PY - 2023 PG - 10 SN - 0753-3322 DO - 10.1016/j.biopha.2023.115548 UR - https://m2.mtmt.hu/api/publication/34153929 ID - 34153929 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [FK138184]; Hungarian Academy of Sciences [BO/00381/21]; Czech Science Foundation [23-04654S]; PTE; European Union - European Social Fund [AOK KA-2022-26]; [EFOP-3.6.1-16-2016-00004] Funding text: The work of M.P. is supported by the Hungarian National Research, Development and Innovation Office (FK138184) and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00381/21) . K.V. was supported by Czech Science Foundation (23-04654S) . The project has been supported the PTE AOK KA-2022-26 grant, and by the European Union, co-financed by the European Social Fund (project name and code: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs, EFOP-3.6.1-16-2016-00004) . AB - Luteolin, naringenin, myricetin, and ampelopsin are abundant flavonoids in nature, and several dietary supplements also contain them at very high doses. After the peroral intake, flavonoids go through extensive presystemic biotransformation; therefore, typically their sulfate/glucuronic acid conjugates reach high concentrations in the circulation. Xanthine oxidase (XO) enzyme is involved in uric acid production, and it also takes part in the elimination of certain drugs (e.g., 6-mercaptopurine). The inhibitory effects of flavonoid aglycones on XO have been widely studied; however, only limited data are available regarding their sulfate and glucuronic acid conjugates. In this study, we examined the impacts of luteolin, naringenin, myricetin, ampelopsin, and their sulfate/glucuronide derivatives on XO-catalyzed xanthine and 6-mercaptopurine oxidations employing in vitro enzyme incubation assays and molecular modeling studies. Our major results/conclusions are the following: (1) Sulfate metabolites were stronger while glucuronic acid derivatives were weaker inhibitors of XO compared to the parent flavonoids. (2) Naringenin, ampelopsin, and their metabolites were weak inhibitors of the enzyme. (3) Luteolin, myricetin, and their sulfates were highly potent inhibitors of XO, and the glucuronides of luteolin showed moderate inhibitory impacts. (4) Conjugated metabolites of luteolin and myricetin can be involved in the inhibitory effects of these flavonoids on XO enzyme. LA - English DB - MTMT ER - TY - JOUR AU - Zsidó, Balázs Zoltán AU - Bayarsaikhan, Bayartsetseg AU - Börzsei, Rita AU - Szél, Viktor AU - Mohos, Violetta Karolin AU - Hetényi, Csaba TI - The Advances and Limitations of the Determination and Applications of Water Structure in Molecular Engineering JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 14 PG - 19 SN - 1661-6596 DO - 10.3390/ijms241411784 UR - https://m2.mtmt.hu/api/publication/34073753 ID - 34073753 N1 - Export Date: 24 October 2023 Correspondence Address: Hetényi, C.; Department of Pharmacology and Pharmacotherapy, Szigeti út 12, Hungary; email: hetenyi.csaba@pte.hu AB - Water is a key actor of various processes of nature and, therefore, molecular engineering has to take the structural and energetic consequences of hydration into account. While the present review focuses on the target–ligand interactions in drug design, with a focus on biomolecules, these methods and applications can be easily adapted to other fields of the molecular engineering of molecular complexes, including solid hydrates. The review starts with the problems and solutions of the determination of water structures. The experimental approaches and theoretical calculations are summarized, including conceptual classifications. The implementations and applications of water models are featured for the calculation of the binding thermodynamics and computational ligand docking. It is concluded that theoretical approaches not only reproduce or complete experimental water structures, but also provide key information on the contribution of individual water molecules and are indispensable tools in molecular engineering. LA - English DB - MTMT ER - TY - JOUR AU - Nemes, Balázs AU - László, Szabolcs AU - Zsidó, Balázs Zoltán AU - Hetényi, Csaba AU - Fehér, Ádám AU - Papp, Ferenc AU - Varga, Zoltán AU - Szőke, Éva AU - Sándor, Zoltán AU - Pintér, Erika TI - Elucidation of the binding mode of organic polysulfides on the human TRPA1 receptor JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 14 PY - 2023 PG - 16 SN - 1664-042X DO - 10.3389/fphys.2023.1180896 UR - https://m2.mtmt.hu/api/publication/34006433 ID - 34006433 N1 - * Megosztott szerzőség AB - Introduction: Previous studies have established that endogenous inorganic polysulfides have significant biological actions activating the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor. Organic polysulfides exert similar effects, but they are much more stable molecules, therefore these compounds are more suitable as drugs. In this study, we aimed to better understand the mechanism of action of organic polysulfides by identification of their binding site on the TRPA1 receptor. LA - English DB - MTMT ER - TY - JOUR AU - Tyukodi, Levente AU - Zsidó, Balázs Zoltán AU - Hetényi, Csaba AU - Kőszegi, Tamás AU - Huber, Imre AU - Rozmer, Zsuzsanna TI - Serum albumin binding studies on antiproliferative cyclic C5-curcuminoid derivatives using spectroscopic methods and molecular modelling JF - JOURNAL OF MOLECULAR STRUCTURE J2 - J MOL STRUCT VL - 1287 PY - 2023 PG - 39 SN - 0022-2860 DO - 10.1016/j.molstruc.2023.135761 UR - https://m2.mtmt.hu/api/publication/33811185 ID - 33811185 N1 - Department of Pharmaceutical Chemistry, University of Pécs, 7624 Pécs, Rókus u. 2., Pécs, Hungary Department of Pharmacology and Pharmacotherapy, Unit of Pharmacoinformatics, University of Pécs, Pécs, Hungary National Laboratory for Drug Research and Development, Budapest, Hungary Department of Laboratory Medicine, Medical School, University of Pécs, Pécs, Hungary János Szentágothai Research Centre, University of Pécs, Pécs, Hungary Export Date: 6 September 2023 CODEN: JMOSB Correspondence Address: Rozmer, Z.; Department of Pharmaceutical Chemistry, 7624 Pécs, Rókus u. 2., Hungary; email: rozmer.zsuzsanna@pte.hu LA - English DB - MTMT ER - TY - JOUR AU - Csenki, Zsolt Imre AU - Bartók, Tibor AU - Bock, Illés AU - Horváth, Levente AU - Lemli, Beáta AU - Zsidó, Balázs Zoltán AU - Angeli, Cserne AU - Hetényi, Csaba AU - Szabó, István AU - Urbányi, Béla AU - Kovács, Melinda AU - Poór, Miklós TI - Interaction of Fumonisin B1, N-Palmitoyl-Fumonisin B1, 5-O-Palmitoyl-Fumonisin B1, and Fumonisin B4 Mycotoxins with Human Serum Albumin and Their Toxic Impacts on Zebrafish Embryos JF - BIOMOLECULES J2 - BIOMOLECULES VL - 13 PY - 2023 IS - 5 PG - 17 SN - 2218-273X DO - 10.3390/biom13050755 UR - https://m2.mtmt.hu/api/publication/33777591 ID - 33777591 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [FK138184]; Source of the National Research, Development and Innovation Fund; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00669/20/4]; Hungarian National Laboratory [RRF-2.3.1-21-2022-00007]; PTE AOK [KA-2022-26]; European Union; European Social Fund [EFOP-3.6.1-16-2016-00004]; Ministry of Innovation and Technology within the framework of the Thematic Excellence Programme 2021; National Defense and Security sub-programme [TKP2021-NVA-22] Funding text: The project is supported by the Hungarian National Research, Development and Innovation Office (FK138184) and by the UNKP-22-5 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (M.P.). This project was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00669/20/4; Z.C.). The support of the Hungarian National Laboratory project, RRF-2.3.1-21-2022-00007 is gratefully acknowledged. Molecular modeling studies of C.H. and B.Z.Z. were supported by the PTE AOK KA-2022-26 grant. The project has also been supported by the European Union and co-financed by the European Social Fund (Project name and code: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs, EFOP-3.6.1-16-2016-00004). This research was supported by the Ministry of Innovation and Technology within the framework of the Thematic Excellence Programme 2021, National Defense and Security sub-programme (TKP2021-NVA-22). LA - English DB - MTMT ER - TY - JOUR AU - Balázs, Orsolya AU - Dombi, Ágnes AU - Zsidó, Balázs Zoltán AU - Hetényi, Csaba AU - Vida, Róbert György AU - Poór, Miklós TI - Probing the Interactions of 31 Mycotoxins with Xanthine Oxidase: Alternariol, Alternariol-3-Sulfate, and α-Zearalenol Are Allosteric Inhibitors of the Enzyme JF - TOXINS J2 - TOXINS VL - 15 PY - 2023 IS - 4 PG - 14 SN - 2072-6651 DO - 10.3390/toxins15040250 UR - https://m2.mtmt.hu/api/publication/33722503 ID - 33722503 N1 - Export Date: 18 January 2024 LA - English DB - MTMT ER -