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IDENTIFICATION OF CYFIP2 ARG87CYS LIGANDS VIA IN SILICO AND IN VITRO APPROACHES
Brain Diseases
Child Development
Molecular Docking
Drug Repositioning
Encefalopatías
Desarrollo Infantil
Acoplamiento Molecular
Reposicionamiento de Medicamentos
Encefalopatias
Desenvolvimento Infantil
Acoplamento Molecular
Reposicionamento de Medicamentos
Autor
Afiliación
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Proteômica Estrutural e Computacional. Curitiba, PR, Brasil.
Resumen en ingles
The advancement of next-generation sequencing has enabled the identification of specific mutations associated with early infantile epileptic encephalopathies (EIEEs). In EIEE, epileptic spasms and seizures that occur since early childhood lead to impaired neurological development. The CYFIP2 p.Arg87Cys variant was recently related to EIEE. CYFIP2 participates in the Wave Regulatory Complex (WRC), which is related to the regulation of actin dynamics. The variant residue is at the interface between the CYFIP2 protein and WAVE1 protein inside the WRC. Thus, the weakening of this interaction induced by the residue modification, which also causes the flexibilization of the loop 80–110 within the CYFIP2 structure, allows the constant activation of the WCR. This study aimed to identify ligands for CYFIP2 p.Arg87Cys and potential therapy targets using in silico in vitro approaches. Models of different CYFIP2 versions were constructed, and molecular docking analyses were conducted. A total of 3946 ligands from the PDE3 and Drugbank databases were screened, leading to the identification of 11 compounds that selectively bind to the variant protein. The impact of binding in CYFIP2 was also evaluated using a thermal stability assay. These findings contribute to a better understanding of CYFIP2’s functional role in pathology and can guide more in vitro experiments, facilitating the development of targeted therapies for CYFIP2-related conditions.
Palabras clave en portugues
CYFIP2Palabras clave en ingles
Epileptic SyndromesBrain Diseases
Child Development
Molecular Docking
Drug Repositioning
Palabras clave
Síndromes EpilépticosEncefalopatías
Desarrollo Infantil
Acoplamiento Molecular
Reposicionamiento de Medicamentos
DeCS
Síndromes EpilépticasEncefalopatias
Desenvolvimento Infantil
Acoplamento Molecular
Reposicionamento de Medicamentos
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