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Previous issue date: 2016-03-18 === Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) === A matriz extracelular (MEC) dos tecidos conjuntivos representa um complexo de numerosos membros de v?rias fam?lias de prote?nas que delineiam sua integridade estrutural e v?rias fun??es fisiol?gicas. As intera??es que ocorrem entre a c?lula e a matriz desempenham um papel preponderante na fixa??o celular e migra??o, assim como tamb?m regulam e promovem a diferencia??o celular e a express?o de genes. O controle dessas intera??es celulares ? crucial para grande parte dos processos biol?gicos. As integrinas s?o uma fam?lia de glicoprote?nas transmembranares, que funcionam como os principais receptores metazo?rios para a ades?o celular, desempenhando um papel central em fun??es de suporte f?sico para a transdu??o de sinais, montagem do citoesqueleto de actina, express?o g?nica e fun??es celulares. Estas glicoprote?nas podem se ligar a glicoprote?nas da matriz extracelular, tal como o col?geno, esta liga??o permite a regula??o e integridade da ades?o celular, migra??o celular e resposta imune. Neste sentido, este trabalho tem como objetivo realizar uma an?lise ab initio da intera??o entre o dom?nio-I da integrina ?2?1 e o col?geno com sequ?ncia GFOGER. A an?lise foi desenvolvida utilizando-se c?lculos de mec?nica qu?ntica, no ?mbito da Teoria do Funcional da Densidade (DFT), com aproxima??es do Gradiente Generalizado (GGA) para descri??o dos efeitos de correla??o e troca. As energias de intera??o entre os res?duos do dom?nio-I ?2 da integrina e os res?duos do col?geno foram calculadas utilizando-se o m?todo de fragmenta??o molecular com capas conjugadas (MFCC). Os resultados encontrados comprovam a import?ncia do ?on met?lico presente na regi?o MIDAS da integrina para a intera??o com a mol?cula do col?geno. A an?lise das energias de intera??o apresentaram os res?duos Glu11, Glu33, Glu55, Arg12, Arg34 e Arg56 da sequ?ncia GFOGER do col?geno, como cruciais para a intera??o com a integrina. J? os res?duos da integrina que demonstraram ser de grande relev?ncia para a intera??o foram a Thr221, Asp219, Asp254 e Glu256. Al?m disso, os resultados tamb?m destacam a import?ncia da altera??o da conforma??o destes res?duos durante a intera??o entre as prote?nas. Logo, o conhecimento das peculiaridades que envolvem a intera??o entre a integrina ?2?1 podem auxiliar a compreens?o de eventos ainda n?o totalmente esclarecidos, bem como fornecer dados relevantes sobre os aspectos particulares apresentados em modelos de muta??es. === The extracellular matrix (ECM) of connective tissues is a complex of many members of
several families of proteins that delineate its structural integrity and various physiological
functions. The interactions occurring between the matrix cell and play a key role in cell
attachment and migration, as well as regulate and promote cell differentiation and gene
expression. The control of these cellular interactions is determinative for most biological
processes. Integrins are a family of transmembrane glycoproteins that function as the main
metazoan receptors for cell adhesion plays a central role in a physical support functions for
signal transduction, cytoskeletal actin assembly, gene expression and cell functions. These
glycoproteins may bind to the extracellular matrix glycoproteins such as collagen, this
connection allows adjustment and integrity of cell adhesion, cell migration and immune
response. Thus, this study aims to perform an ab initio analysis of the interaction between the
domain-I integrin ?2?1 and collagen with GFOGER sequence. The analysis was carried out
using quantum mechanical calculations within Density Functional Theory (DFT) with the
Generalized Gradient Approximation (GGA) for describing the exchange and correlation
effects. The energies of interaction between domain-I ?2 integrin residues and collagen
residues were calculated using the Molecular Fragmentation with Conjugated Caps (MFCC).
The results demonstrate the importance of metal ion present in the MIDAS region of the
integrin for interaction with the collagen molecule. The analysis showed the interaction
energies residues Arg12, Glu33, Arg34, Glu55, and Arg56 GFOGER sequence of collagen, as
important to the interaction with the integrin. In the residues of integrin shown to be of great
relevance to the interaction were Thr221, Asp219, Asp254 and Glu256. Moreover, the results
also highlight the importance of changing the conformation of these residues during the
interaction between the proteins. These results can aid understanding of events involving the
interaction between integrin ?2?1 and collagen as well as provide relevant data on special
aspects presented in mutations models.
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