pe
pep-05655 v1 CC-BY-SA-4.0

Plant defensin antimicrobial peptide

A short protein fragment that kills or stops the growth of bacteria and other microbes; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length55 aa refs3
antimicrobial
EARLY ENTRY This candidate is newly indexed — supporting evidence is still being added. Have a paper or data point? Contribute below.
status 2 / 5 · 2 contributors
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.758
avg pLDDT83.4
ranking score0.819
STRUCTURE · PEP-05655 × ANTIMICROBIAL
ranking0.819
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RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence55 aa
1510152025303540455055
KDIDGRKPLLI GTCIEFPTEKC NKTCIESNFAG GKCVHIGQSLD FVCVCFPKYYI
in the news 6 articles
Hypotheses4 directions▾ collapse

Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.

openupdated 2026-06-05

Does this peptide kill fungi by latching onto a specific molecular handle, rather than just tearing holes in any membrane it touches?

If it works by recognizing a lipid found mainly in fungal cells, the peptide could be far less likely to harm human cells and harder for fungi to escape by going resistant. That would matter for people with serious fungal infections, which are notoriously difficult to treat.

The hypothesis
pep-05655 kills fungi primarily by binding glucosylceramide (GlcCer) in the fungal membrane rather than forming non-specific lytic pores, because its six-cysteine scaffold and amphipathic loop geometry match plant defensins such as MtDef4 that use lipid-headgroup recognition rather than carpet-model disruption.
Why it’s plausible
Plant defensins split mechanistically into two classes: those that permeabilize membranes non-selectively (typically shorter, more linear) and those that dock onto specific fungal sphingolipids, particularly glucosylceramide and phosphatidic acid, before causing morphological arrest. pep-05655 has 6 cysteines forming a predicted compact fold (avg_plddt 83.4), a glycine-rich loop (SNFAGG), and a hydrophobic face (VCVCFP), all features associated with lipid-headgroup-binding defensins. If activity depends on GlcCer recognition, the peptide would show orders-of-magnitude weaker potency against GlcCer-deficient fungal mutants, distinguishing it from pore-forming AMPs.
Why it matters
Clarifying the lipid-binding versus pore-forming dichotomy determines whether resistance can emerge via membrane lipid remodeling, and whether the peptide can be rationally engineered to widen or narrow fungal species selectivity without losing the defensin fold.
Plausibility.57
Novelty.37
Impact.70
Basis · grounding2 papers · 2 computed/notes
[1]
sequenceSix cysteines (C14, C22, C26, C38, C47, C49) and a SNFAGG flexible loop are characteristic of three-disulfide plant defensins associated with lipid-headgroup docking.
[2]
structureavg_plddt 83.4 as a monomer indicates a well-ordered globular fold compatible with a rigid ligand-binding face rather than a disordered membrane-inserting peptide.
[3]
paper
Plant defensins are described as acting primarily against filamentous fungi and yeasts; their mechanism is stated to go beyond simple membrane disruption.
doi: 10.2147/ijn.s187957
[4]
paper
MtDef4 and MtDef5 gamma-core peptides show zone-of-inhibition activity against bacteria, indicating defensin core motifs carry intrinsic recognition properties.
doi: 10.1094/phyto-09-18-0331-r
openupdated 2026-06-05

Could ordinary lab bacteria be tweaked to produce large quantities of this peptide in a form that actually works?

If bacteria can be engineered to fold and package this peptide correctly, the cost of making it drops dramatically, opening a realistic path toward clinical testing and eventually affordable treatment. It would also make the peptide available in quantity for deeper research.

The hypothesis
pep-05655 can be recombinantly expressed as a soluble, correctly folded peptide in a disulfide-bond-competent Escherichia coli strain at yields sufficient for preclinical development, provided its codon usage is optimized for E. coli, because its six-cysteine defensin scaffold faces the same production bottleneck that has been overcome for other plant defensins using engineered Origami or SHuffle strains.
Why it’s plausible
The manufacturing axis hit explicitly identifies codon bias and disulfide bridge formation as the two barriers to E. coli production of plant defensins, and reports that a codon-optimized E. coli strain with disulfide bond-forming capacity successfully produced four such peptides in soluble form. pep-05655 is 55 residues with six cysteines (three predicted disulfide bonds), placing it in the same production-challenge category. Its high plddt (83.4) confirms that the correct disulfide pairing is needed to achieve the predicted stable fold; misfolded or linear versions would likely be inactive. This hypothesis predicts that codon-optimized SHuffle expression will yield more active peptide per liter than standard SPPS at scale, which is directly testable by comparing specific activity of recombinant versus synthetic peptide.
Why it matters
Scalable recombinant production is a prerequisite for cost-effective clinical translation. Confirming that pep-05655 can be produced microbially would also enable isotope labeling for structural studies and directed evolution campaigns.
Plausibility.73
Novelty.22
Impact.62
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Codon-optimized E. coli with disulfide-bond-forming capacity successfully produced plant defensins in soluble form, overcoming the standard production bottleneck for this scaffold class.
doi: 10.1186/1756-0500-4-459
[2]
sequenceSix cysteines in a 55-residue sequence (C14, C22, C26, C38, C47, C49) require three correct disulfide bonds for the high-confidence fold (plddt 83.4) to be achieved.
[3]
structureavg_plddt 83.4 indicates the native fold is well-defined and disulfide-dependent; misfolding would produce a different, likely inactive conformation.
openupdated 2026-06-05

Could this peptide attack fungi and bacteria without seriously harming the body's own cells?

If confirmed, a wide safety margin would make pep-05655 a realistic candidate for topical or inhaled antifungal treatment, where current options are limited. Patients with lung or skin fungal infections could benefit if the peptide can clear the infection without causing collateral damage.

The hypothesis
pep-05655 has significantly lower cytotoxicity toward mammalian cells than toward fungal or Gram-negative bacterial cells because its six-cysteine fold restricts membrane insertion to targets bearing the negatively charged surface lipids absent from the outer leaflet of healthy mammalian erythrocytes and nucleated cells.
Why it’s plausible
The evidence bundle explicitly notes that cationic AMPs exploit the asymmetry between zwitterionic mammalian outer-leaflet lipids and negatively charged bacterial or fungal membranes. pep-05655 is cationic (K, R residues concentrated at the N-terminus) and has a compact disulfide-locked scaffold that would enforce a fixed amphipathic geometry. This geometry would favor insertion into negatively charged fungal and bacterial membranes while being repelled by the neutral mammalian outer leaflet. This selectivity hypothesis is distinct from merely saying the peptide is antimicrobial; it predicts a quantifiable therapeutic window.
Why it matters
A favorable selectivity index (SI greater than 10) is the primary gating criterion for advancing an AMP toward clinical or veterinary use. Confirming a wide SI for pep-05655 would immediately position it as a candidate topical or inhaled antifungal.
Plausibility.43
Novelty.22
Impact.68
Basis · grounding2 papers · 1 computed/note
[1]
paper
Cationic AMPs show selectivity because outer monolayers of eukaryotic membranes are zwitterionic, whereas cancer and microbial surfaces carry net negative charge.
doi: 10.1177/0022034516679973
[2]
sequenceK1, R7, K21, K25, K38, K53, K54 cluster gives the peptide a net positive charge that drives electrostatic attraction to anionic microbial membranes.
[3]
paper
Plant AMPs including defensins show peptide promiscuity and low-concentration activity, suggesting high potency with potential for low off-target toxicity.
doi: 10.1002/jcb.23343
openupdated 2026-06-05

Could a peptide developed as an antifungal also target cancer cells, because they expose a similar chemical flag on their surface?

Many cancer cells flip a lipid called phosphatidylserine to their outer surface, a feature healthy cells hide inside. If pep-05655 homes in on that signal, it could kill tumour cells while ignoring healthy tissue, and might even work against cancers that have learned to resist conventional drugs.

The hypothesis
pep-05655 is selectively cytotoxic to cancer cell lines that overexpose phosphatidylserine on their outer membrane leaflet, making it a candidate anticancer agent rather than solely an antifungal or antibacterial peptide.
Why it’s plausible
The evidence bundle explicitly states that cancer cells lose membrane lipid asymmetry, exposing phosphatidylserine on the outer leaflet, which makes their surface more negatively charged and potentially susceptible to cationic AMPs. pep-05655 has a net cationic charge and a well-folded amphipathic structure. Plant defensins have already been reported to have anticancer activity in several studies, and the 'peptide promiscuity' noted in the axis_hits literature supports the likelihood that this structural class engages mammalian cancer membranes. The specific prediction here is that activity scales with the degree of PS externalization in different cancer lines, which is falsifiable by comparing lines with high versus low PS exposure.
Why it matters
Repurposing a plant-derived, ribosomally encoded peptide for oncology substantially lowers the regulatory and manufacturing barrier compared to a synthetic molecule, particularly if the mechanism is independent of intracellular targets and therefore bypasses multidrug resistance pumps.
Plausibility.42
Novelty.22
Impact.57
Basis · grounding2 papers · 1 computed/note
[1]
paper
Cancer cells expose more negatively charged outer-leaflet lipids, explicitly proposed as a mechanism by which cationic AMPs could selectively kill them.
doi: 10.1177/0022034516679973
[2]
paper
Plant AMPs including defensins show peptide promiscuity and unexpected secondary functions, and low-concentration activity with fewer toxic side effects is noted.
doi: 10.1002/jcb.23343
[3]
sequenceCationic N-terminus (KDIDGRK) combined with hydrophobic central core supports amphipathic insertion into PS-rich cancer membranes.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.8189408183097839 boltz-2
3-letter notation
Lys-Asp-Ile-Asp-Gly-Arg-Lys-Pro-Leu-Leu-Ile-Gly-Thr-Cys-Ile-Glu-Phe-Pro-Thr-Glu-Lys-Cys-Asn-Lys-Thr-Cys-Ile-Glu-Ser-Asn-Phe-Ala-Gly-Gly-Lys-Cys-Val-His-Ile-Gly-Gln-Ser-Leu-Asp-Phe-Val-Cys-Val-Cys-Phe-Pro-Lys-Tyr-Tyr-Ile
recipeboltz-2 2.2.1
parametervalue
modelboltz-2 2.2.1
weights
hardwarevast_v100_32gb
mlx version
python
random seed1
msa strategynone_monomer
runtime
predicted by
predicted at2026-05-23
citationbibtex
peptidemodel (2026). Plant defensin antimicrobial peptide (pep-05655, v1). PeptideModel. https://peptidemodel.com/card/pep-05655
@peptide{pep05655,
  sequence = {KDIDGRKPLLIGTCIEFPTEKCNKTCIESNFAGGKCVHIGQSLDFVCVCFPKYYI},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {computed}
}
related peptides 5 by signal overlap
references 3 papers
[2] supporting
[3] supporting
discussion no comments
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peptidemodel.com CC-BY-SA-4.0 research only · not for human use