Abstract

YOSA-REYES, Juvenal; CLAVIJO-BURITICA, Diana Carolina; ESTEVEZ-BRETON RIVEROS, Carlos Manuel  and  ACEVEDO, Orlando Emilio. Semiempirical methods for the rapid evaluation of frontier orbitals in the classification of agonists and antagonists of the NR1 subunit of the iGluR-NMDA receptors. Univ. Sci. [online]. 2011, vol.16, n.1, pp.5-14. ISSN 0122-7483.

The ionotropic glutamate receptors activated by N-Methyl-D-Aspartate (iGluR-NMDA) are of great importance in pharmacology since they are involved in neurodegenerative and neuropsychiatric disorders; they even participate in processes such as synaptic plasticity that are essential for memory formation. Subunit NR1 iGluRs-NMDA is of paramount importance for the appropriate activation of this type of receptors; in fact, many of the pharmaceutical products studied for the abovementioned disorders are targeted specifically to the NR1 subunit. Previous studies have shown that the lowest energy unoccupied molecular orbital (LUMO) can be used as a parameter to estimate the agonist and antagonist activity of the NR1subunit. Objective. Evaluate the semiemprical method CNDO for the rapid calculation of the LUMO energy with the aim of preparing a simple model for the in silico design of new pharmacological substances. Materials and methods. 168 molecules with agonist and antagonist activity in the NR1 subunit were selected. Energy of each structure was optimized and then we calculated the energy of the frontier orbital, the LogP, total energy, capacity of forming hydrogen bonds, binding energy, and dipolar moment. Results. We demonstrate that LUMO energy is enough for discriminating agonist and antagonist molecules of the NR1 subunit and that the CNDO method evaluates these properties in a rapid and efficient way. Conclusions. The CNDO method facilitates a rapid calculation, enabling a future development of effective procedures for the characterization of potential pharmacological substances acting on this particular site.

Keywords : iGluR-NMDA; LUMO; agonist; antagonist; CNDO.

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