Estudo de estruturas, interações e reconhecimento molecular em carboidratos utilizando simulação computacional.
PEREIRA, Cristina Saldanha. Study of structures, interactions and molecular recognition in carbohydrates using computer simulation.. 2004. 145 f. Tese (Doutorado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2004.
Pereira, Cristina Saldanha
In this work, computer simulation methods were applied to investigate glucose-derived carbohydrates in solution at atomistic resolution. The carbohydrates considered were: trehalose and cyclodextrins. The disaccharide trehalose is well known for its bioprotective properties. Produced in large amounts in organisms able to survive extremely damaging conditions trehalose plays its protective role by stabilizing biostructures such as proteins and lipid membranes. In the present study, molecular-dynamics simulations were used to investigate the interaction of trehalose with a protein and a membrane. To investigate the interaction trehalose-protein molecular-dynamics simulations of the protein lysozyme in solution have been carried out in the presence and in the absence of trehalose at room temperature. The results show that the trehalose molecules cluster and move towards the protein, but do neither completely expel water from its surface, nor form hydrogen bonds. Furthermore, the coating by trehalose does not significantly reduce the conformational fluctuations of the protein. The interaction trehalose-membrane was investigated performing simulations of a lipid bilayer in the absence and in the presence of trehalose at two different concentrations and temperatures. The results show that trehalose is able to minimize the disruptive effect of elevated temperature and stabilize the bilayer structure. Trehalose is found to interact directly with the bilayer through hydrogen bonds. However, the water molecules at the bilayer surface are not completely replaced. At high temperature the protective effect of trehalose is correlated with an increase in the number of hydrogen bonds with the bilayer and of trehalose molecules bridging three or more lipid molecules. Cyclodextrins are cyclic oligosaccharides presenting a cavity able to accommodate and modify the properties of a huge variety of molecules. Their structural behavior in solution is determinant for the complexation abilities. Molecular dynamics simulations have been performed in solution for the three natural (α, β and γ) cyclodextrins at room temperature. Results show that the conformational flexibility in solution is mainly defined by variations in the ring backbone of these molecules. Interglucose secondary hydrogen bonds are present in solution and show a very dynamical character, where alternative hydrogen bonds to water molecules are present. Water molecules were found to exist inside the cavities and present residence times in this region that is dependent on the size of the cyclodextrin molecule.