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Curr Med Chem ; 30(15): 1776-1796, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36453498

RESUMEN

BACKGROUND: The Brugada syndrome (BrS) is a heart rhythm condition that is commonly associated with a strong predisposition for sudden cardiac death. Malignant ventricular arrhythmias could occur secondary to the dysfunction of the cardiac sodium voltage-gated Na(v)1.5 channel (SCN5A). OBJECTIVE: This study aimed to perform a multiparametric computational analysis of the physicochemical properties of SCN5A mutants associated with BrS using a set of bioinformatics tools. METHODS: In-house algorithms were calibrated to calculate, in a double-blind test, the Polarity Index Method (PIM) profile and protein intrinsic disorder predisposition (PIDP) profile of each sequence, and computer programs specialized in the genomic analysis were used. RESULTS: Specific regularities in the charge/polarity and PIDP profile of the SCN5A mutant proteins enabled the re-creation of the taxonomy, allowing us to propose a bioinformatics method that takes advantage of the PIM profile to identify this group of proteins from their sequence. CONCLUSION: Bioinformatics programs could reproduce characteristic PIM and PIDP profiles of the BrS-related SCN5A mutant proteins. This information can contribute to a better understanding of these altered proteins.


Asunto(s)
Síndrome de Brugada , Humanos , Síndrome de Brugada/genética , Síndrome de Brugada/metabolismo , Biología Computacional , Electrocardiografía/métodos , Predisposición Genética a la Enfermedad , Proteínas Mutantes/genética , Proteínas Mutantes/metabolismo , Mutación , Canal de Sodio Activado por Voltaje NAV1.5/genética , Canal de Sodio Activado por Voltaje NAV1.5/metabolismo
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