Fate of amine-based selenenyl sulfides during interaction with glutathione reductase: a molecular dynamics perspective

TL;DR

This study develops force field parameters for selenenyl sulfides and uses molecular dynamics simulations to explore their interactions with glutathione reductase, revealing key influences of amino nitrogen on binding behavior.

Contribution

It provides the first force field parameters for selenenyl sulfides and applies MD simulations to investigate their interaction with glutathione reductase.

Findings

A 200 ns MD simulation was performed on RSeSG.

Amino nitrogen significantly influences interaction with GR.

Substituents on nitrogen affect binding at the catalytic site.

Abstract

In the search for small organoselenium-based mimics of the glutathione peroxidase (GPx) enzyme, it has been observed that selenenyl sulfides (RSeSG) derived from amine-based GPx mimics have the potential to be reduced at the catalytic site of glutathione reductase (GR), thereby enhancing the catalytic efficiency of these mimics in biological systems. However, molecular insights into these interactions are lacking due to the absence of force field parameters for Se-S containing compounds. In this study, we present force field parameters for selenenyl sulfides with a phenyl selenide backbone developed using the General Amber Force Field (GAFF). Employing these parameters, a 200 ns molecular dynamics (MD) simulation of RSeSG was performed. The results indicate that both the amino nitrogen and its substituent significantly influence the interaction of RSeSG at the catalytic site of GR.