Struktura glykosyltransferázy toxinu TcdB s nativním substrátem

Bc. Náth Vozábal

Bachelor's thesis

Structure of TcdB Toxin Glycosyltransferase with Native Substrate

Abstract:

Tato bakalářská práce se zaměřuje na využití AlphaFoldu, programu pro predikci terciární struktury proteinů s využitím hlubokého učení a neuronových sítí, spolu se simulacemi molekulové dynamiky k in silico studiu experimentálně neznámého komplexu glykosyltransferázy toxinu TcdB a malé GTPásy RhoA. Nejprve se predikovaly modely pomocí AlphaFoldu, poté se komplex doplnil o substrát a kofaktory. Následně se sestavené modely otestovaly a vybraly se vhodné struktury pro molekulárně dynamickou simulaci. Výsledné trajektorie se analyzovaly a posoudila se stabilita celého komplexu. Získané poznatky mohou dále sloužit pro pochopení a další studium patogeneze bakterie Clostridioides difficile.

Abstract:

This bachelor thesis focuses on the use of AlphaFold, a program for predicting tertiary structure of proteins using deep learning and neural networks, together with molecular dynamics simulations to study in silico an experimentally unknown complex of the glycosyltransferase toxin TcdB and the small GTPase RhoA. Models were first predicted using AlphaFold, then the complex was augmented with substrate and cofactors. Subsequently, the assembled models were tested and suitable structures were selected for molecular dynamics simulations. The resulting trajectories were analyzed and the stability of the whole complex was assessed. The obtained knowledge can be further used to understand and next study the pathogenesis of the bacterium Clostridioides difficile.

Keywords

Clostridioides difficile, C. difficile, glykosyltransferáza, AlphaFold, molekulová dynamika, glucosyltransferase, molecular dynamics

Language used: Czech

Date on which the thesis was submitted / produced: 18. 5. 2023

Thesis defence

• Date of defence: 28. 6. 2023
• Supervisor: RNDr. Petr Kulhánek, Ph.D.
• Reader: Mgr. Jan Novotný, Ph.D.

Masaryk University

Faculty of Science

Bachelor programme / field:
Biochemistry / Bioinformatics