Key result
Molecular dynamics simulations revealed that peptides inhibiting renin move out of critical binding pockets, whereas they remain intact in ACE pockets due to metal ion coordination.
In-silico molecular dynamics simulations reveal that bioactive peptides targeting ACE have stable binding due to metal ion coordination, whereas those targeting renin lose potency by shifting out of critical binding pockets, providing insights for designing dual RAS-targeting peptides.
No immediate clinical implications; leaves open peptide optimization for RAS pending experimental validation.
) were subjected to molecular dynamics simulation. Our results identified that the peptides inhibiting renin, tends to move out of the binding pockets (S1' S2') which is critical for potent binding and occupies the less important pockets (S4 and S3). This could possibly be the reason for its low potency. Whereas, the same peptides targeting ACE, tends to be intact in the pocket because of the metal ion coordination and there is an ample room to improve on its efficacy. Our results further pave way for the biochemist, medicinal chemist to design dual peptides targeting the RAS effectively. Communicated by Ramaswamy H. Sarma.
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Gunalan et al. (2019) studied this question. Bioactive peptides targeting RAS enzymes was evaluated on Binding pocket dynamics. Molecular dynamics simulations revealed that peptides inhibiting renin move out of critical binding pockets, whereas they remain intact in ACE pockets due to metal ion coordination.
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