Original title: Kombinovaný QM/MM popis interakcí organokovových komplexů aktivních v léčbě rakoviny s oligomerními modely DNK, RNK a bílkovin
Translated title: Combined QM/MM decsription of interaction of organometallic complexes active in anticancer treatment with oligomer models of DNA, RNA, and proteins
Authors: Pavolko, Juraj ; Burda, Jaroslav (advisor) ; Šanda, František (referee)
Document type: Bachelor's theses
Year: 2026
Language: slo
Abstract: [eng] [cze]
This bachelor thesis focuses on the theoretical study of the proton transfer mechanism within the active site of thioredoxin reductase 1 (TrxR1). To determine energy barriers and verify the reaction mechanism, we used hybrid QM/MM simulations and Steered Molecular Dynamics (SMD) at both semi-empirical (PM7) and Density Functional The- ory (DFT) levels. The results showed that the originally proposed path via the Cysteine 50 residue is energetically unfavorable. However, we identified a thermodynamically pre- ferred path involving direct transfer to Cysteine 55, which is stabilized by the enzyme's environment. The thesis also analyzes the methodological limitations of non-equilibrium dynamics, specifically the thermodynamic paradox, contributing to more accurate mode- ling of enzymatic reactions Táto práca sa zaoberá teoretickým štúdiom mechanizmu prenosu protónu v aktívnom mieste enzýmu tioredoxín reduktázy 1 (TrxR1). Na stanovenie energetických bariér a ve- rifikáciu mechanizmu sme využili hybridné QM/MM simulácie a metódu riadenej mole- kulovej dynamiky (SMD) na úrovni semiempirickej metódy PM7 aj funkcionálu hustoty (DFT). Výsledky ukázali, že pôvodne predpokladaný prenos cez rezíduum Cysteín 50 je energeticky nevýhodný. Naopak, identifikovali sme termodynamicky preferovanú cestu priamym prenosom na Cysteín 55, ktorá stabilizuje prostredie enzýmu. Práca zároveň analyzuje metodické limity nerovnovážnej dynamiky, konkrétne termodynamický para- dox, čím prispieva k presnejšiemu modelovaniu enzymatických reakcií.
Keywords: MM; organometallic complexes|DNA|RNA|proteins|anti-cancer treatment|DFT|QM; MM; organokovové komplexy|DNK|RNK|proteiny|protirakovinné účinky|DFT|QM

Institution: Charles University Faculties (theses) (web)
Document availability information: Available in the Charles University Digital Repository.
Original record: http://hdl.handle.net/20.500.11956/211077

Permalink: http://www.nusl.cz/ntk/nusl-780669


The record appears in these collections:
Universities and colleges > Public universities > Charles University > Charles University Faculties (theses)
Academic theses (ETDs) > Bachelor's theses