<?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>0120-6230</journal-id>
<journal-title><![CDATA[Revista Facultad de Ingeniería Universidad de Antioquia]]></journal-title>
<abbrev-journal-title><![CDATA[Rev.fac.ing.univ. Antioquia]]></abbrev-journal-title>
<issn>0120-6230</issn>
<publisher>
<publisher-name><![CDATA[Facultad de Ingeniería, Universidad de Antioquia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0120-62302021000100117</article-id>
<article-id pub-id-type="doi">10.17533/udea.redin.20200368</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Molecular dynamics simulations of Alzheimer's BACE1 and BACE2 transmembrane domains in neurons: Impact of cholesterol]]></article-title>
<article-title xml:lang="es"><![CDATA[Simulaciones de dinámica molecular de dominios transmembranales de BACE1 y BACE2 del Alzheimer en neuronas: Impacto del colesterol]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cruz-Jiménez]]></surname>
<given-names><![CDATA[Juan Carlos]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Mercado-Montoya]]></surname>
<given-names><![CDATA[Marcela]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ostos-Ortíz]]></surname>
<given-names><![CDATA[Carlos Eduardo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Hernández-Valdivieso]]></surname>
<given-names><![CDATA[Alher Mauricio]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad de Los Andes Departamento de Ingeniería Biomédica ]]></institution>
<addr-line><![CDATA[Bogotá ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad de Antioquia Facultad de Ingeniería Programa de Bioingeniería]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad de Antioquia Facultad de Ciencias Exactas y Naturales ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>03</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>03</month>
<year>2021</year>
</pub-date>
<numero>98</numero>
<fpage>117</fpage>
<lpage>128</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0120-62302021000100117&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0120-62302021000100117&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0120-62302021000100117&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[ABSTRACT Molecular dynamic (MD) simulation is an approach frequently employed in computational biology for exhaustive sampling of the protein-ligand conformational space. Hence, it is useful for structural analysis and the study of molecular interactions. In this study, we report on a MD simulation protocol to understand the dynamics of &#946;-secretase 1 (BACE1) and 2 (BACE2), widely known to play a critical role in the etiology of Alzheimer&#8217;s disease, by a structure change evaluation of their transmembrane domains while inserted in a simulated neural membrane system. We considered two different levels in membrane cholesterol content. Because there is no evidence supporting the capacity of BACE1 and BACE2 to exist as a dimer, single and double (BACE1/BACE1, BACE2/BACE2, BACE1/BACE2) systems, either in parallel or antiparallel orientation, were prepared for each run. Analysis of tridimensional structure of BACE1 and BACE2, after 10ns of MD simulation, revealed a correlation between higher cholesterol levels and both peptide refolding and changes in the secondary structure of both transmembrane domains in single and double systems. Interestingly, our results also indicate a potential interaction in the double system BACE2/BACE2, particularly when the domains had an antiparallel orientation.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[RESUMEN Las simulaciones de dinámica molecular (MD) son una aproximación que se emplea frecuentemente en biología computacional para muestreo exhaustivo del espacio conformacional proteína-ligando. Por este motivo, son útiles para el análisis estructural y el estudio de interacciones moleculares. En este estudio, reportamos sobre el protocolo de simulación MD para entender la dinámica de las &#946;-secretasa 1 (BACE1) y 2 (BACE2), los cuales se sabe ampliamente que juegan un papel transcendental en la enfermedad de Alzheimer. Esto se logró evaluando los cambios estructurales en los dominios a través de la membrana mientras se encontraban insertos en un complejo de membrana neuronal simulada. Aquí se consideraron dos niveles en el contenido de colesterol de la membrana. Debido a que no existe evidencia reportada soportando la capacidad de dimerización de BACE1 y BACE2, se prepararon sistemas sencillos y dobles (BACE1/BACE1, BACE2/BACE2, BACE1/BACE2) tanto en orientación paralela como antiparalela para cada corrida. Después de 10ns de simulación MD, el análisis de la estructura tridimensional reveló una correlación entre los altos niveles de colesterol y tanto el replegamiento de péptidos como los cambios en la estructura secundaria de ambos dominios transmembranales en sistemas simples y dobles. Interesantemente, nuestros resultados también indican un marcado potencial de interacción en el Sistema doble BACE2/BACE2, particularmente cuando los dominios asumen una orientación antiparalela.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Modal analysis]]></kwd>
<kwd lng="en"><![CDATA[complex modes]]></kwd>
<kwd lng="en"><![CDATA[structural analysis]]></kwd>
<kwd lng="en"><![CDATA[molecular interaction]]></kwd>
<kwd lng="es"><![CDATA[Análisis modal]]></kwd>
<kwd lng="es"><![CDATA[modos complejos]]></kwd>
<kwd lng="es"><![CDATA[análisis estructural]]></kwd>
<kwd lng="es"><![CDATA[interacción molecular]]></kwd>
</kwd-group>
</article-meta>
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