Bioinformatics Insights on the Physicochemical Properties of SCN5A Mutant Proteins Associated with the Brugada Syndrome

Abstract

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.

Keywords: SCN5A; SCN5A gene; SNC5A mutant proteins; bioinformatics; intrinsic disorder predisposition profile; polarity index method profile; structural proteomics.