Issue 5, 2023

Mapping the structure–activity landscape of non-canonical peptides with MAP4 fingerprinting

Abstract

Peptide structure–activity/property relationship (P-SA/PR) studies focus on understanding how the structural variations of peptides influence their biological activities and other functional properties. This knowledge accelerates the rational design and optimisation of peptide-based drugs, biomaterials, or diagnostic agents. These studies examine peptide structures from their primary sequences, essentially encoded from the 20 amino acids. Current approaches often exclude peptide libraries with post-translational and synthetic modifications. The molecular fingerprint MAP4 was recently developed to map complex molecules' sequence/structure diversity, including peptides. This study used structure–activity landscape modelling to conduct the P-SA/PR studies of an exemplary dataset of 223 antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA). To this end, we employed the MAP4 fingerprint to represent the chemical structures of the peptides, study their relationship(s) with the antibacterial activity, and seek the potential activity cliff(s). We identified critical residues and structural motifs that play a crucial role in the anti-MRSA activity of the peptides. This is the first computational study to systematically explore the activity landscape of peptides with non-canonical residues, emphasising the quantification of structural similarity.

Graphical abstract: Mapping the structure–activity landscape of non-canonical peptides with MAP4 fingerprinting

Supplementary files

Article information

Article type
Paper
Submitted
31 maj 2023
Accepted
31 aug 2023
First published
01 sep 2023
This article is Open Access
Creative Commons BY license

Digital Discovery, 2023,2, 1494-1505

Mapping the structure–activity landscape of non-canonical peptides with MAP4 fingerprinting

E. López-López, O. Robles, F. Plisson and J. L. Medina-Franco, Digital Discovery, 2023, 2, 1494 DOI: 10.1039/D3DD00098B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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