Abstract

ALVAREZ, Yesid et al. Molecular modeling and structural analysis of variant I684S in the TYK2 enzyme and its relation with the susceptibility to psoriasis. Rev. acad. colomb. cienc. exact. fis. nat. [online]. 2023, vol.47, n.182, pp.8-21.  Epub Mar 04, 2025. ISSN 0370-3908.  https://doi.org/10.18257/raccefyn.1694.

Psoriasis is an immune-mediated chronic inflammatory disease in which the IL-23/Th17 axis directs the pathogenic process. In a Colombian population, the regulation of the immune system and susceptibility to the development of psoriasis was associated with the non-synonymous variant I684S in TYK2. To understand the effect of this mutation, we used molecular modeling with the structure predictor Phyre2, which allowed us to recognize 3D folding and, thus, unify the model with the crystallized structures of the different subunits that have been reported as isolated subunits. This final model was refined with two software programs and the best model scored with energetic and stereo-chemical values was selected for subsequent simulation. The molecular simulation was done with the semi-empirical method of the Spartan 18' software and the Austin Model 1 force field for the neighborhood region that includes position 684 where the energetic and electronic surface calculation was made under a quantum mechanical approach. The results showed that the models presented 3D changes at the topological level in the wild TYK2 enzyme compared with the I684S mutation in the hydrogen bonding patterns and the electronic structure with an increase in the electronic density of the mutation favoring phosphorylation of kinases in signal transduction and immune dysregulation.

Keywords : Psoriasis; Tyrosine kinase; Molecular modeling; Simulation; Quantum mechanics.

        · abstract in Spanish     · text in Spanish     · Spanish ( pdf )