pe
pep-05484 v1 CC-BY-SA-4.0

Natural germ-killing peptide

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

statuscomputed targetANTIMICROBIAL length60 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
pTM0.207
avg pLDDT39.3
ranking score0.356
STRUCTURE · PEP-05484 × ANTIMICROBIAL
ranking0.356
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence60 aa
151015202530354045505560
EEECWMKGKCRLVCKNDEDS VTRCSNRKRCCILSRYLTIV PMTIDRMLPWTTPQVTQGDS
in the news 6 articles
Hypotheses3 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

Could the unusual chemistry of this peptide make it hit dangerous skin and wound infections while leaving other bacteria alone?

Many antibiotics kill broadly, wiping out beneficial bacteria alongside harmful ones. If this peptide's charge profile really does steer it toward Gram-positive bugs like MRSA and drug-resistant Enterococcus, it could become a narrower, more targeted treatment option for those infections, with less collateral damage to the patient's microbiome.

The hypothesis
pep-05484 preferentially kills Gram-positive bacteria over Gram-negative bacteria because the anionic N-terminal EEE block is repelled by the dense LPS of Gram-negative outer membranes but is tolerated by the lipoteichoic-acid surface of Gram-positive organisms, where the hydrophobic core segment dominates membrane engagement.
Why it’s plausible
Gram-negative LPS presents an outer membrane barrier with a highly anionic surface and divalent-cation cross-links that can repel anionic peptide domains. Gram-positive bacteria lack an outer membrane and expose lipoteichoic acid, which is less uniformly charged and creates a more permeable surface for mixed-charge peptides. The EEE N-terminus of pep-05484 would be specifically disadvantaged against the Gram-negative LPS barrier but less penalized when directly encountering the cytoplasmic membrane of Gram-positive organisms, allowing the hydrophobic and cationic central core to reach and disrupt the membrane.
Why it matters
Characterizing the Gram-selectivity profile of pep-05484 would determine whether it is most useful against Gram-positive pathogens such as MRSA and Enterococcus, informing its clinical niche relative to existing antibiotics.
Plausibility.50
Novelty.43
Impact.55
Basis · grounding1 paper · 1 computed/note
[1]
sequenceEEE at positions 1-3 constitutes an anionic N-terminal block unusual in canonical AMPs; hydrophobic/cationic core at residues ~7-28
[2]
paper
Electrostatic attraction to negatively charged bacterial surface drives AMP activity; Gram-negative LPS presents distinct charge barrier vs. Gram-positive lipoteichoic acid
doi: 10.1177/0022034516679973
openupdated 2026-06-05

Could the negative end of this peptide act like a safety latch that only releases when the peptide is near a bacterial surface, not a human one?

Most bacteria-killing peptides are indiscriminate and can damage red blood cells, limiting their clinical use. If the three-glutamate block on this peptide really does hold back its activity until it hits a bacterial surface, it might cause less harm to human tissue, making it a safer candidate for treating infections directly in the body.

The hypothesis
The N-terminal anionic cluster (EEE, residues 1-3) of pep-05484 suppresses membrane disruption activity at physiological pH but is converted to a net-cationic amphipathic state upon interaction with the acidic surface charge of Gram-negative lipopolysaccharide, enabling pH-independent but charge-environment-dependent membrane insertion.
Why it’s plausible
Standard cationic AMP activity is driven by electrostatic attraction to the negatively charged bacterial membrane. pep-05484 carries an unusual three-glutamate N-terminal block (EEE) that would repel bacterial membranes if uncompensated. However, LPS presents a concentrated negative charge field and divalent cation bridges; this local environment could rearrange the peptide's charge distribution or induce a conformational shift so that the central hydrophobic segment ILSRYLTIVPM (residues 31-41) and the positively charged residues (K7, K10, R12, R26, K28) become accessible for membrane insertion. The very low avg_plddt (39.3) supports intrinsic disorder, which is a hallmark of charge-dependent fold-on-binding behavior in host-defense peptides.
Why it matters
If the anionic cluster acts as a regulatory switch rather than a liability, pep-05484 would have an inherently lower toxicity window toward mammalian cells (which also carry surface negative charge but lack dense LPS) than most cationic AMPs, making it a candidate for lower-haemotoxicity AMP design.
Plausibility.38
Novelty.43
Impact.57
Basis · grounding1 paper · 2 computed/notes
[1]
sequencePositions 1-3 are E,E,E; K at 7,10; R at 12,26,28; hydrophobic core at approximately residues 31-41 (ILSRYLTIVPM)
[2]
paper
Cationic AMPs require amphipathic conformation and electrostatic attraction to negatively charged bacterial surfaces; zwitterionic eukaryotic membranes partly explain selectivity
doi: 10.1177/0022034516679973
[3]
structureavg_plddt 39.3 indicates intrinsic disorder as a free monomer, consistent with fold-on-binding mechanism
openupdated 2026-06-05

If only the middle section of this peptide does the real work, could chemists cut away the rest and still get a useful drug at a much lower price?

Long peptides are expensive and slow to manufacture, which often blocks otherwise promising compounds from becoming real medicines. If a shorter, stripped-down version of this peptide holds onto most of its bacteria-killing ability, it could become affordable enough to actually develop, opening a path from lab curiosity to clinical candidate.

The hypothesis
Because pep-05484 is 60 residues long and therefore near the SPPS length limit, an engineered disulfide-stripped analog retaining only the KCRLVCK (positions 10-16, preserving C-X3-C spacing) and the hydrophobic core ILSRYLTIVPM can recapitulate at least half the antimicrobial activity of the full-length peptide at one-third the synthesis cost.
Why it’s plausible
The central segment of pep-05484 from approximately residue 10 to 41 contains all the cationic (K10, R12, K28), cysteine (C10, C14, C23, C33-34), and hydrophobic (ILSRYLTIVPM) features that drive canonical AMP activity. The N-terminal anionic EEE block (1-3) and the C-terminal polar tail WTTPQVTQGDS (49-60) are compositionally anomalous for an AMP and may represent vestigial parent-protein scaffold rather than functional pharmacophore. Truncation analogs removing these flanking regions would reduce length below 30 residues, making them economically viable for SPPS and removing the EEE repulsion that may attenuate potency.
Why it matters
A potent 25-30 residue analog would be manufacturable at one-third the cost of the full 60-residue peptide, transforming pep-05484 from a curiosity into a development candidate.
Plausibility.37
Novelty.33
Impact.60
Basis · grounding2 papers · 1 computed/note
[1]
sequenceC-terminal WTTPQVTQGDS (residues 50-60) is polar and lacks cationic or hydrophobic character typical of AMP active regions; N-terminal EEE is atypical for AMPs
[2]
paper
SPPS cost-prohibitive above ~50 amino acids; 60-residue length of pep-05484 is at the practical upper limit
doi: 10.1038/s41467-023-37003-z
[3]
paper
High manufacturing cost ($100-$600/g) is the single largest barrier limiting AMP development and clinical translation
doi: 10.1038/nbt1267
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.3557605743408203 boltz-2
3-letter notation
Glu-Glu-Glu-Cys-Trp-Met-Lys-Gly-Lys-Cys-Arg-Leu-Val-Cys-Lys-Asn-Asp-Glu-Asp-Ser-Val-Thr-Arg-Cys-Ser-Asn-Arg-Lys-Arg-Cys-Cys-Ile-Leu-Ser-Arg-Tyr-Leu-Thr-Ile-Val-Pro-Met-Thr-Ile-Asp-Arg-Met-Leu-Pro-Trp-Thr-Thr-Pro-Gln-Val-Thr-Gln-Gly-Asp-Ser
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). Natural germ-killing peptide (pep-05484, v1). PeptideModel. https://peptidemodel.com/card/pep-05484
@peptide{pep05484,
  sequence = {EEECWMKGKCRLVCKNDEDSVTRCSNRKRCCILSRYLTIVPMTIDRMLPWTTPQVTQGDS},
  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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