<?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>0120-2804</journal-id>
<journal-title><![CDATA[Revista Colombiana de Química]]></journal-title>
<abbrev-journal-title><![CDATA[Rev.Colomb.Quim.]]></abbrev-journal-title>
<issn>0120-2804</issn>
<publisher>
<publisher-name><![CDATA[Departamento de Química,  Universidad Nacional de Colombia.]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0120-28042023000100003</article-id>
<article-id pub-id-type="doi">10.15446/rev.colomb.quim.v52n1.110374</article-id>
<title-group>
<article-title xml:lang="en"><![CDATA[Dynamics and Energetics of a Bromodomain in complex with bromosporine from Leishmania donovani]]></article-title>
<article-title xml:lang="es"><![CDATA[Dinámica y Energética de un Bromodominio en complejo con bromosporina de Leishmania donovani]]></article-title>
<article-title xml:lang="pt"><![CDATA[Dinâmica e energética de um bromodomínio em complexo com bromosporina de Leishmania donovani]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ropón-Palacios]]></surname>
<given-names><![CDATA[Georcki]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Chenet-Zuta]]></surname>
<given-names><![CDATA[Manuel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramos-Galarza]]></surname>
<given-names><![CDATA[Jean]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Gervacio-Villarreal]]></surname>
<given-names><![CDATA[Alfonzo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Otazu]]></surname>
<given-names><![CDATA[Kewin]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Cárdenas-Cárdenas]]></surname>
<given-names><![CDATA[Reyna]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Casillas-Muñoz]]></surname>
<given-names><![CDATA[Fidel]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidade Federal de Alfenas-UNIFAL-MG  ]]></institution>
<addr-line><![CDATA[Alfenas Minas Gerais ]]></addr-line>
<country>Brazil</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Universidad Nacional Tecnologica del Lima Sur UNTELS  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
<country>Peru</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad Nacional de la Amazonía Peruana  ]]></institution>
<addr-line><![CDATA[Iquitos ]]></addr-line>
<country>Peru</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad de Guadalajara Departamento de Farmacobiología Centro Universitario de Ciencias Exactas e Ingenierías]]></institution>
<addr-line><![CDATA[Guadalajara Jalisco]]></addr-line>
<country>Mexico</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>04</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>04</month>
<year>2023</year>
</pub-date>
<volume>52</volume>
<numero>1</numero>
<fpage>3</fpage>
<lpage>9</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0120-28042023000100003&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0120-28042023000100003&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0120-28042023000100003&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract Leishmaniasis continues to be a neglected tropical disease, affecting people and animals and causing significant economic losses. Therefore, there is interest in the study and evaluation of new drug targets. In fact, it has been shown that by interfering with lysine-reading proteins such as bromodomain (BMD) there is a decrease in parasite survival. In this study, we researched the dynamics and energetics of the Leishmania donovani BMD in complex with bromosporin, which is considered to be a pan-inhibitor of BMDs, with the aim of understanding the molecular recognition mechanism. Molecular dynamics (MD) and non-equilibrium free energy calculation guided by steered molecular dynamics (SMD) simulations showed that the BMD has three flexible amino acid regions and bromosporin exhibiting various recognition states during the interaction. These results corroborate the promiscuity of bromosporin for energetically favourable sites, with the possibility of expanding its inhibition to other bromodomains. Furthermore, these results suggest that Van der Waals interactions have more relevance for complex recognition and residues ASN-87 and TRP-93 are key in forming hydrophobic and H-bond interactions, respectively. This research provides new insights for understanding the recognition mechanism, dynamics and energetics of the complex for the development of new therapeutic strategies.]]></p></abstract>
<abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen La leishmaniasis sigue siendo una enfermedad tropical desatendida, que afecta a personas y animales y causa importantes pérdidas económicas. De ahí el interés por estudiar y evaluar nuevas dianas farmacológicas. De hecho, se ha demostrado que al interferir con proteínas lectoras de lisina como el bromodominio ("bromodomain", BMD) se produce una disminución de la supervivencia del parásito. En este artículo estudiamos la dinámica y la energética del BMD de Leishmania donovani en complejo con bromosporina, que se considera un pan-inhibidor de BMD, con el objetivo de comprender el mecanismo de reconocimiento molecular. Las simulaciones de dinámica molecular (DM) y el cálculo de energía libre de no-equilibrio guiado por dinámica molecular de estiramiento (DMS) mostraron que BMD tiene tres regiones de aminoácidos flexibles y la bromosporina presenta varios estados de reconocimiento durante la interacción. Estos resultados corroboran la promiscuidad de la bromosporina por sitios energéticamente favorables, siendo posible expandir su inhibición a otros bromodominios. Además, los resultados sugieren que las interacciones de Van der Waals tienen más relevancia para el reconocimiento del complejo y los residuos ASN-87 y TRP-93 son clave en la formación de interacciones hidrofóbicas y de puentes de hidrógeno, respectivamente. Esta investigación proporciona nuevos conocimientos para comprender el mecanismo de reconocimiento molecular, la dinámica y la energética del complejo para el desarrollo de nuevas estrategias terapéuticas.]]></p></abstract>
<abstract abstract-type="short" xml:lang="pt"><p><![CDATA[Resumo A leishmaniose continua a ser uma doença tropical negligenciada, que afeta os seres humanos e os animais e causa perdas econômicas significativas. Daí o interesse em estudar e avaliar novos alvos de medicamentos. De fato, a interferência com proteínas leitoras de lisina, como o bromo domínio ("bromodomain", BMD), tem demonstrado diminuir a sobrevivência do parasita. Neste trabalho, estudamos a dinâmica e a energética do BMD de Leish-mania donovani em complexo com a bro-mosporina, considerada um pan-inibidor da BMDs, com o objetivo de compreender o mecanismo de reconhecimento molecular. As simulações de dinâmica molecular (MD) e cálculo de energia livre de não-equilíbrio guiada por dinâmica molecular esticamento (MDS) mostraram que o BMD tem três regiões de aminoácidos flexíveis e que a bromosporina apresenta vários estados de reconhecimento durante a interação. Esses resultados corroboram a promiscuidade da bromosporina para locais energeticamente favoráveis, possibilitando a expansão de sua inibição para outros bromodomínios. Além disso, os resultados sugerem que as interações de Van der Waals são mais relevantes no momento do reconhecimento do complexo e os resíduos ASN-87 e TRP-93 são fundamentais na formação de interações hidrofóbicas e de ligações de hidrogênio, respectivamente. Essa pesquisa fornece novos insights para compreender o mecanismo de reconhecimento, a dinâmica e a energética do complexo para o desenvolvimento de novas estratégias terapêuticas.]]></p></abstract>
<kwd-group>
<kwd lng="en"><![CDATA[Bromodomain]]></kwd>
<kwd lng="en"><![CDATA[bromosporine]]></kwd>
<kwd lng="en"><![CDATA[molecular dynamics]]></kwd>
<kwd lng="en"><![CDATA[free energy]]></kwd>
<kwd lng="es"><![CDATA[Bromodominio]]></kwd>
<kwd lng="es"><![CDATA[bromos-porina]]></kwd>
<kwd lng="es"><![CDATA[dinámica molecular]]></kwd>
<kwd lng="es"><![CDATA[energía libre]]></kwd>
<kwd lng="pt"><![CDATA[Bromodomínio]]></kwd>
<kwd lng="pt"><![CDATA[bromos-porina]]></kwd>
<kwd lng="pt"><![CDATA[dinâmica molecular]]></kwd>
<kwd lng="pt"><![CDATA[energia livre]]></kwd>
</kwd-group>
</article-meta>
</front><back>
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