Evidence map›Paper›PMID 39085646›Full record

ArticleNature biomedical engineering2024

Deep mutational scanning and machine learning for the analysis of antimicrobial-peptide features driving membrane selectivity.

Justin R Randall, Luiz C Vieira, Claus O Wilke, Bryan W Davies

Abstract read
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Artificial intelligence catalyzes antimicrobial peptide design.Synthetic and systems biotechnology · 2027
    Review
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  13. Painting Peptides With Antimicrobial Potency Through Deep Reinforcement Learning.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  14. Resurfacing promotes antibacterial activity of a lipid A-binding nanobody.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Justin R RandallDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Luiz C VieiraDepartment of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.
Claus O WilkeDepartment of Integrative Biology, The University of Texas at Austin, Austin, TX, USA.
Bryan W DaviesDepartment of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. bwdavies@austin.utexas.edu.ORCID http://orcid.org/0000-0002-2046-0341

Funding

Investigating nanobodies to target multidrug resistant bacterial pathogensR01AI148419 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI DAVIES, BRYAN WILLIAM · 2020 to 2023
$2.8M
A High-Throughput Molecular Platform for Antimicrobial Discovery and StudyR01AI125337 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI DAVIES, BRYAN WILLIAM · 2016 to 2020
$2.0M
Investigation of capsule interactions that promote antimicrobial peptide activityR21AI159203 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI DAVIES, BRYAN WILLIAM · 2021 to 2022
$429k
CLC NIH HHS C0000008Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) AI125337Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) AI148419Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) AI159203NIAID NIH HHS R01 AI125337NIAID NIH HHS R01 AI148419NIAID NIH HHS R21 AI159203
6 · The paper itself

Abstract

Many antimicrobial peptides directly disrupt bacterial membranes yet can also damage mammalian membranes. It is therefore central to their therapeutic use that rules governing the membrane selectivity of antimicrobial peptides be deciphered. However, this is difficult even for short peptides owing to the large combinatorial space of amino acid sequences. Here we describe a method for measuring the loss or maintenance of antimicrobial-peptide activity for thousands of peptide-sequence variants simultaneously, and its application to Protegrin-1, a potent yet toxic antimicrobial peptide, to determine the positional importance and flexibility of residues across its sequence while identifying variants with changes in membrane selectivity. More bacterially selective variants maintained a membrane-bound secondary structure while avoiding aromatic residues and cysteine pairs. A machine-learning model trained with our datasets accurately predicted membrane-specific activities for over 5.7 million Protegrin-1 variants, and identified one variant that showed substantially reduced toxicity and retention of activity in a mouse model of intraperitoneal infection. The high-throughput methodology may help elucidate sequence-structure-function relationships in antimicrobial peptides and inform the design of peptide-based synthetic drugs.

Indexed as

Antimicrobial Cationic PeptidesMachine LearningAmino Acid SequenceAnimalsAntimicrobial PeptidesCell MembraneFemaleMiceMicrobial Sensitivity TestsMutationStructure-Activity RelationshipAntimicrobial Cationic PeptidesAntimicrobial Peptidesprotegrin-1

Identifiers

PMID39085646
PMCPMC12044605

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.