Estudo da dinâmica de solvatação de peptídeos por QM/MM
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Data
2015-12-11
Autores
Almeida, Glauco Garrido [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
Trabalhos experimentais e teóricos desenvolvidos nos últimos anos evidenciaram a capacidade de alcoóis e polialcoóis em mudar características energéticas em proteínas. No entanto, o mecanismo responsável por esse efeito não está totalmente elucidado. Tomando como exemplo o dipeptídeo de alanina, foram realizadas simulações QM/MM em água, etanol e mistura 60-40 % em volume de água-etanol. A molécula de dipeptídeo foi descrita em nível de cálculo quântico MP2/aug-cc-pVDZ. Em solução, apenas confórmeros αR e PPII foram encontrados na população de equilíbrio. A diferença de energia livre em solução αR PPII é determinada pelo balanço entre energia interna do soluto e energia de interação. Para o dipeptídeo de alanina, qualquer fator que aumente a energia de interação soluto-solvente favorece o aumento da população de αR. Por outro lado fatores que diminuam esse valor, como a adição de etanol, aumentam a população de PPII. Os resultados indicam solvatação preferencial para o sistema, evidenciado pela formação majoritária da primeira camada de solvatação por moléculas de água (na mistura), embora seja possível encontrar moléculas de etanol em pequenas quantidades ao redor do grupo carboxílico da extremidade N-terminal e, cadeias metílicas laterais. Todavia, o comportamento parece não afetar a diferença na estabilidade de equilíbrio conformacional.
Recent papers, both experimental and theoretical, have highlighted the capacity of alcohols and polyalcohol in modifying the energy landscape in proteins. However, the mechanism underlying this effect is not fully elucidated. Taking as a model-system the alanine dipeptide, QM/MM calculations were performed in water, ethanol and solution 60-40% (volume) water-ethanol. The dipeptide molecule was described by MP2/aug-cc-pVDZ level. In solution, only αR and PPII conformers were found in the conformational equilibrium population. The free energy difference in solution αR PPII is determined by the interplay between internal energy and the interaction energy. It has been found that, for alanine dipeptide, any factor that increases the solute-solvent interaction energy also promotes an increasing on αR stability, moreover factors that decreases this value, such as the addition of ethanol molecules, increases the PPII stability. The results points to a preferential solvation behavior for the system, as evidenced by the composition of the first solvation shell in the mixture mainly populated by water molecules, although it is possible to find small concentration of ethanol molecules around the carboxyl group of the N-terminal end and around methylic side chains. However, this behavior does not seem to affect the differential conformational stability.
Recent papers, both experimental and theoretical, have highlighted the capacity of alcohols and polyalcohol in modifying the energy landscape in proteins. However, the mechanism underlying this effect is not fully elucidated. Taking as a model-system the alanine dipeptide, QM/MM calculations were performed in water, ethanol and solution 60-40% (volume) water-ethanol. The dipeptide molecule was described by MP2/aug-cc-pVDZ level. In solution, only αR and PPII conformers were found in the conformational equilibrium population. The free energy difference in solution αR PPII is determined by the interplay between internal energy and the interaction energy. It has been found that, for alanine dipeptide, any factor that increases the solute-solvent interaction energy also promotes an increasing on αR stability, moreover factors that decreases this value, such as the addition of ethanol molecules, increases the PPII stability. The results points to a preferential solvation behavior for the system, as evidenced by the composition of the first solvation shell in the mixture mainly populated by water molecules, although it is possible to find small concentration of ethanol molecules around the carboxyl group of the N-terminal end and around methylic side chains. However, this behavior does not seem to affect the differential conformational stability.
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Palavras-chave
QM/MM, Alanina, Peptídeos, Interação de hidrogênio, Etanol, Alanine, Peptides, Hydrogen bond, Ethanol