Engineering protein fragments via evolutionary and protein –protein interaction algorithms: de novo design of peptide inhibitors for FOF1‐ATP synthase

Enzyme subunit interfaces have remarkable potential in drug design as both target and scaffold for their own inhibitors. We show an evolution ‐driven strategy for thede  novo design of peptide inhibitors targeting interfaces of theEscherichia  coli FoF1 ‐ATP synthase as a case study. The evolutionary algorithm ROSE was applied to generate diversity‐oriented peptide libraries by engineering peptide fragments from ATP synthase interfaces. The resulting peptides were scored with PPI‐Detect, a sequence‐based predictor of protein–protein inter actions. Two selected peptides were confirmed byin  vitro inhibition and binding tests. The proposed methodology can be widely applied to design peptides targeting relevant interfaces of enzymatic complexes.

Source: FEBS Letters - November 19, 2020 Category: Biochemistry Authors: Yasser B. Ruiz ‐Blanco, Luis Pablo Ávila‐Barrientos, Enrique Hernández‐García, Agostinho Antunes, Guillermin Agüero‐Chapin, Enrique García‐Hernández Tags: Research Article Source Type: research