Estudo computacional por dinâmica molecular do flavonóide Sakuranetina na interface água-lipídio
Data
2021-12-14
Autores
Freire, Vitor Torres 
Orientadores
Siqueira, Leonardo José Amaral de
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Nos últimos anos, com o aumento de microrganismos resistentes aos antibióticos tradicionais e com o aumento do índice de doenças cardiovasculares, respiratórias e carcinomas na população é necessário cada vez mais compreender o mecanismo de ação de compostos de origem natural que possam ajudar a enfrentar esses novos desafios. A sakuranetina (SAK), um flavonóide encontrado em diversos vegetais, apresenta capacidade anti-inflamatória, antiprotozoária, antiviral, antitumoral e antimicrobiana, porém, seu mecanismo de interação com células ainda não é bem estabelecido na literatura. Simulações computacionais por Dinâmica Molecular em modelos simplificados de membrana celular são uma ferramenta viável, de baixo custo e bem fundamentada na literatura para ajudar a compreender esses fenômenos. Neste trabalho uma molécula de sakuranetina foi disposta no vácuo e empurrada através de uma monocamada de dipalmitoilfosfatidilcolina (DPPC), um fosfolipídio comum em membranas biológicas, até uma fase aquosa, simulando uma membrana biológica. Medidas físico-químicas e termodinâmicas foram tomadas nesse processo. Verificou-se que o custo energético para que a sakuranetina realize esse processo é de aproximadamente 150 kJ/mol, relativamente mais alto do que de outras substâncias; que a posição energeticamente mais favorável nesse trajeto é próximo do fim das cadeias apolares do DDPC e que uma vez nessa posição ela assume configurações espaciais específicas, interagindo de forma diferente com os elementos do sistema e expandindo o filme da monocamada, aumento em até 4,2% a área ocupada por molécula de lipídio. O estudo, portanto, permitiu um detalhamento de como se dá o processo de interação deste flavonóide com membranas biológicas.
In recent years, with the increase in microorganisms resistant to traditional antibiotics and the increasing rate of cardiovascular, respiratory and carcinomas in the population, it is necessary to better understand the mechanism of action of compounds of natural origin that can help us face these new challenges. Sakuranetin (SAK), is a flavonoid found in several plants, with anti-inflammatory, antiprotozoal, antiviral, antitumor and antimicrobial properties, however, its mechanism of interaction with cells is not well established in the literature yet. Computational simulations by Molecular Dynamics in simplified cell membrane models are a viable, low-cost and well-founded tool in the literature to help understand these phenomena. In this work, a sakuranetin molecule was placed in vacuum and pushed through a monolayer of dipalmitoyl phosphatidylcholine (DPPC), a common phospholipid in biological membranes, to an aqueous phase, simulating a biological membrane. Physicochemical and thermodynamic measurements were taken in this process. It was found that the energy cost for sakuranetin to carry out this process is approximately 150 kJ/mol, relatively higher than for other substances; that the most energetically favorable position in this path is near the end of the DDPC nonpolar chains and that once in this position it assumes specific spatial configurations, interacting differently with the system and expanding the monolayer film, increase by up to 4,2% the area occupied by lipid molecule. The study, therefore, allowed a detailing of how the interaction process of this flavonoid with biological membranes takes place.
In recent years, with the increase in microorganisms resistant to traditional antibiotics and the increasing rate of cardiovascular, respiratory and carcinomas in the population, it is necessary to better understand the mechanism of action of compounds of natural origin that can help us face these new challenges. Sakuranetin (SAK), is a flavonoid found in several plants, with anti-inflammatory, antiprotozoal, antiviral, antitumor and antimicrobial properties, however, its mechanism of interaction with cells is not well established in the literature yet. Computational simulations by Molecular Dynamics in simplified cell membrane models are a viable, low-cost and well-founded tool in the literature to help understand these phenomena. In this work, a sakuranetin molecule was placed in vacuum and pushed through a monolayer of dipalmitoyl phosphatidylcholine (DPPC), a common phospholipid in biological membranes, to an aqueous phase, simulating a biological membrane. Physicochemical and thermodynamic measurements were taken in this process. It was found that the energy cost for sakuranetin to carry out this process is approximately 150 kJ/mol, relatively higher than for other substances; that the most energetically favorable position in this path is near the end of the DDPC nonpolar chains and that once in this position it assumes specific spatial configurations, interacting differently with the system and expanding the monolayer film, increase by up to 4,2% the area occupied by lipid molecule. The study, therefore, allowed a detailing of how the interaction process of this flavonoid with biological membranes takes place.