Simulação molecular de proteínas com nós geométricos

Abstract

The role of knots in proteins remains undefined. Some studies suggest an impact on stability, however, they have difficulties in comparing systems to assess this effect. In this study, were produced and analyzed molecular dynamic trajectories of two variants of ornithine transcarbamoylase (OTC), only one of which has a 31 knot, in order to evaluate the relative stability of the two molecules. Root mean square desviation (RMSD) showed equilibrated structures for the produced trajectories, and root mean square fluctuation (RMSF) showed subtle differences in flexibility. In the knot moiety, the knotted protein did not show a great deal of fluctuation at any temperature. For the unknotted protein, the residue GLY243 showed a high fluctuation in the corresponding moiety. The fraction of native contacts (Q) showed a similar profile at all temperatures, with the greatest decrease by 436K. The investigation of conformational behavior with principal component analysis (PCA) and dynamic cross-correlation map (DCCM) showed that knotted protein is less likely to undergo changes in its conformation under the conditions employed compared to unknotted. PCA data showed that the unknotted protein had greater dispersion in its conformations, which suggests that it has a greater capacity for conformation transitions in response to thermal changes. DCCM graphs comparing the 310K and 436K temperatures showed that the knotted protein had less change in its correlation and anti-correlation movements, indicating stability structural compared to the unknotted. The local reactivity descriptors used investigation of electronic structure characteristics showed differences for the identical residues in the knot moiety. This suggests that the reactivity descriptors obtained by quantum calculations can be used in the investigation of the effect that the node can have on the electronic structure of knotted protein.