Evaluación in silico de toxinas peptídicas de origen animal con efecto antagonista sobre la actividad del Receptor - N-Metil-D-Aspatarto (NMDA)

Abstract

The N-methyl-D-aspartate receptor (NMDAR) constitutes the main subtype of glutamate receptors, involved in physiological processes such as neuronal development, transmission and synaptic plasticity, and in numerous pathological conditions such as ischemic damage, chronic pain, psychosis, and other degenerative disorders. The NMDAR has a structural topology consisting of four subunits mainly of the GluN1 and GluN2(A-B) type. The ionotropic NMDAR corresponds to an ionic-cation channel, permeable mainly to calcium ion. An excessive increase in calcium influx via NMDAR generates excitotoxicity which translates into neuronal damage and death. Based on the above, it is essential to search for molecules that generate interaction with the receptor and specifically with the GluN2B subunit, modulate the activity of the receptor-channel and can be recycled or eliminated by the organism. The present thesis proposal proposes the design and in silico characterization of peptides derived from animal toxins with potential targeting of the NMDAR. The design included the use of computational analysis tools, alignments and docking and molecular dynamics simulations, which allowed predicting the three-dimensional structure of a series of peptide toxins and proposing peptides derived from them as potential NMDAR ligands