Molecular modeling of the antigen-antibody complex to the investigations of autoimmune demyelinating diseases

Abstract

The multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease that causes axonal damage. The molecular mechanisms involved in the evolution of this disease still unknown by the scientific community, even though the research efforts involving experimental autoimmune encephalomyelitis - EAE. The immunologic system has a key role on the development of the MS. The literature reports that the autoreactive antibodies participate against the myelin oligodendrocyte glycoprotein (MOG) and against the myelin basic protein (MBP). In this project, Computational Molecular Modeling will be employed to elucidate the antibody interactions with antigens from the myelin. Homology Modeling, Molecular Docking, Molecular Dynamic Simulation and Quantum Dynamics are the set of computational methodologies to be used in this study. The correlation between theoretical and experimental (Atomic Force Microscopy, AFM) results is obtained statistically by using Steered Molecular Dynamics, SMD. Computational approaches will allow a detailed quantification of the forces involved in humoral molecular response from the EAE and MS. Also, the reactive sites of the studied molecules will be predicted since the difficult to its interpretation experimentally. (AU)