Counteraction of urea-induced protein denaturation by Trimethylamine N-oxide

• Main Author: VANTARAKI, CHRISTINA
• Format: Others
• Language: English
• Published: Uppsala universitet, Molekyl- och kondenserade materiens fysik 2019
• Subjects: Atom and Molecular Physics and Optics; Atom- och molekylfysik och optik
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-390487

A common consequence of protein denaturation is the loss of biological activity. Natural osmolytes such as Trimethylamine N-oxide (TMAO) contribute to protein folding, whereas other osmolytes such as urea act as an agent in the denaturation of proteins. Many studies have shown that denaturation of proteins could occur for certain concentrations of urea, however, this effect could be prevented with the presence of Trimethylamine N-oxide (TMAO) molecules. The aim of the present study is to find out the mechanism of TMAO as a protein stabilizer against urea. Firstly, Molecular Dynamics simulations were carried out for 1, 8, 27 and 64 TMAO molecules. The time-average location of the TMAO molecules during the simulation was studied by the partial density. These simulations examine if TMAO is amphiphilic molecule, i.e contains both hydrophobic and hydrophilic parts. However, these results might not be representative due to bad statistics. Secondly, an experiment ran at BESSY II at Helmholtz-Zentrum Berlin using X-ray Photoelectron Spectroscopy in liquids. In this experiment, Lauryldimethylamine oxide(LDAO) was used instead of Trimethylamine N-oxide (TMAO) due to some practical reasons. The behaviour of urea and LDAO molecule was studied when these molecules were in different and same solutions. The purpose of this experiment is to find out the mechanism of LDAO against urea. Finally, LDAO interacts with urea and a possible mechanism between them is suggested. A common consequence of protein denaturation is the loss of biological activity. Natural osmolytes such as Trimethylamine N-oxide (TMAO) contribute to protein folding, whereas other osmolytes such as urea act as an agent in the denaturation of proteins. Many studies have shown that denaturation of proteins could occur for certain concentrations of urea, however, this effect could be prevented with the presence of the Trimethylamine N-oxide (TMAO) molecules. The aim of the present study is to find out the mechanism of TMAO as a protein stabilizer against urea. Firstly, Molecular Dynamics simulations were carried out for 1, 8, 27 and 64 TMAO molecules. The time-average location of TMAO molecules during the simulation was studied by the partial density. These simulations examine if TMAO is amphiphilic molecule, i.e contains both hydrophobic and hydrophilic parts. However, these results might not be representative due to bad statistics. Secondly, an experiment ran at BESSY II at Helmholtz-Zentrum Berlin using X-ray Photoelectron Spectroscopy in liquids. In this experiment, Lauryldimethylamine oxide (LDAO) was used instead of Trimethylamine N-oxide (TMAO) due to some practical reasons. The behaviour of urea and LDAO molecule was studied when these molecules were in different and same solutions. The purpose of this experiment is to find out the mechanism of LDAO against urea. Finally, LDAO interacts with urea and a possible mechanism between them is suggested. === <p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p><p></p>