Caracterização da interação da quitosana com epirrubicina por modelagem molecular

Abstract

This work is part of the study of the interaction between the chitosan biopolymer and the epirubicin chemotherapy through the analysis of the results of simulations performed in the GROMACS program. The literature review provided the basis for the use of molecular dynamics and the choice of chitosan and epirubicin to model our systems. The procedures adopted involved the generation of the topology of molecules in the OPLS-AA (Optimized potentials for liquid simulations-all-atom) force field, which is a robust force field having the advantage, offered by the option (AA), of treating the atoms separately. All methodology used has been adjusted for this force field. First, the assignment of atom loads was made by calculating loads RESP (Restrained Eletrostatic Potential). Later, the loads of negative hydrogen atoms were replaced by values consulted in the force field assigning the same load value to identical groups. The micro-species curves of epirubicin obtained in the MARVINSKETCH program provided the majority structure at pH (7.4; 9; 10). After the preparation of the PDB files of the structures it was made the calculation of molecular anchorage in the autodock progrgram. Then three systems formed by a chitosan filament and an epirubicin molecule were modeled. The molecular dynamics calculations for these systems were aimed at characterizing how chitosan interacts with epirrubicin. However, the results showed that the molecules are inert and the systems are very unstable. The discussion of the results was reinforced by calculations of the number of hydrogen bonds and the minimum distance between the chitosan and the epirrubicin. In order to deepen the analysis of the results, a system with four times the chitosan mass was modelled. The results confirmed that the complex is not formed and showed the importance of performing a previous characterization by molecular dynamics, before the execution of experimental procedures.