<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>0370-3908</journal-id>
<journal-title><![CDATA[Revista de la Academia Colombiana de Ciencias Exactas, Físicas y Naturales]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. acad. colomb. cienc. exact. fis. nat.]]></abbrev-journal-title>
<issn>0370-3908</issn>
<publisher>
<publisher-name><![CDATA[Academia Colombiana de Ciencias Exactas, Físicas y Naturales]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0370-39082023000100008</article-id>
<article-id pub-id-type="doi">10.18257/raccefyn.1694</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Modelamiento molecular y análisis estructural de la variante I684S en la enzima TYK2 y su relación con la propensión a la psoriasis]]></article-title>
<article-title xml:lang="en"><![CDATA[Molecular modeling and structural analysis of variant I684S in the TYK2 enzyme and its relation with the susceptibility to psoriasis]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Alvarez]]></surname>
<given-names><![CDATA[Yesid]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Soto-Ospina]]></surname>
<given-names><![CDATA[Alejandro]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Villegas-Lanau]]></surname>
<given-names><![CDATA[Andrés]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Araque]]></surname>
<given-names><![CDATA[Pedronel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Naranjo]]></surname>
<given-names><![CDATA[Carlos Andrés]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Uribe]]></surname>
<given-names><![CDATA[Esteban]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Jiménez]]></surname>
<given-names><![CDATA[Sol]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Vásquez]]></surname>
<given-names><![CDATA[Eisa]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Bedoya]]></surname>
<given-names><![CDATA[Gabriel de Jesús]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Velásquez]]></surname>
<given-names><![CDATA[Margarita]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad de Antioquia Genética Molecular (GenMol) Facultad de Ciencias Exactas y Naturales]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Corporación Universitaria Unilasallista Grupo de Investigaciones en Alimentos (GRIAL) Facultad de Ingenierías]]></institution>
<addr-line><![CDATA[ Antioquia]]></addr-line>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad EIA Grupo de Investigación e Innovación en Formulaciones Químicas ]]></institution>
<addr-line><![CDATA[Envigado ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad CES, Medellín Dermatología ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Universidad CES Epidemiología ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af6">
<institution><![CDATA[,Universidad de Antioquia Centro de Investigaciones Dermatológicas CIDERM, Sección de Dermatología]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>03</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>03</month>
<year>2023</year>
</pub-date>
<volume>47</volume>
<numero>182</numero>
<fpage>8</fpage>
<lpage>21</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0370-39082023000100008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0370-39082023000100008&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0370-39082023000100008&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen La psoriasis es una enfermedad inflamatoria crónica inmunomediada en la que el eje IL-23/Th17 dirige el proceso patogénico. En la regulación del sistema inmunitario la propensión al desarrollo de la psoriasis en una población colombiana se asoció con la variante no sinónima I684S en TYK2. En el estudio funcional del efecto de la variante a nivel molecular, se hizo la modelación molecular de la enzima a partir de su secuencia primaria, lo que permite reconocer el plegamiento tridimensional y unificar así el modelo con las estructuras cristalizadas de las diferentes subunidades de la enzima que han sido reportadas como aisladas y sin conexión. Este modelo final se refinó utilizando dos programas y se seleccionó el mejor para la simulación posterior según la puntuación de los valores energéticos y estereoquímicos. La simulación molecular se hizo con el método semiempírico del programa Spartan 18' y el campo de fuerza del Austin Model 1 para la región vecinal que incluye la posición 684 en donde se hizo el cálculo energético y de superficie electrónica bajo un enfoque mecánico cuántico. Los resultados evidenciaron que los modelos presentaron cambios tridimensionales a nivel topológico de la enzima TYK2 silvestre y la mutación I684S en los patrones del enlace de hidrógeno y en la estructura electrónica, con un aumento de la densidad electrónica en la mutación que favorece la fosforilación de quinasas en la transducción de la señal y la desregulación inmunológica.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract 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.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Psoriasis]]></kwd>
<kwd lng="es"><![CDATA[Tirosina quinasa]]></kwd>
<kwd lng="es"><![CDATA[Modelamiento molecular]]></kwd>
<kwd lng="es"><![CDATA[Simulación]]></kwd>
<kwd lng="es"><![CDATA[Mecánica cuántica]]></kwd>
<kwd lng="en"><![CDATA[Psoriasis]]></kwd>
<kwd lng="en"><![CDATA[Tyrosine kinase]]></kwd>
<kwd lng="en"><![CDATA[Molecular modeling]]></kwd>
<kwd lng="en"><![CDATA[Simulation]]></kwd>
<kwd lng="en"><![CDATA[Quantum mechanics]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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