pe
pep-05595 v1 CC-BY-SA-4.0

Brevinin-2GHb antimicrobial peptide

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

statusbioassayed targetANTIMICROBIAL length57 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 · 0 verified on platform
prediction metrics boltz-2 2.2.1
ipTM0.000
pTM0.317
avg pLDDT61.8
ranking score0.558
STRUCTURE · PEP-05595 × ANTIMICROBIAL
ranking0.558
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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
sequence57 aa
151015202530354045505557
GTISLLCQEDERGADEDDE GEMTEEQKRSLLGLLKGAG KTLLSAGLNKIACKLTGKC
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 trimming the inactive part of a natural peptide turn it into a useful weapon against one of the world's most dangerous drug-resistant bacteria?

Acinetobacter baumannii is on the WHO's most-critical list of superbugs, and doctors are running out of options. If this hypothesis holds, a stripped-down version of a frog-derived peptide could become a compact, synthesizable drug candidate that targets this pathogen, giving researchers a new starting point for antibiotic development.

The hypothesis
Truncation of Brevinin-2GHb to only the C-terminal cationic amphipathic helix and Rana box (approximately residues 31-57: SLLGLLKGAGKTLLSAGLNKIACKLTGKC) will restore or exceed the antimicrobial potency of canonical brevinin-2 family members against multidrug-resistant Acinetobacter baumannii, while retaining low hemolytic activity.
Why it’s plausible
The C-terminal segment (residues 31-57) carries all the canonical features of active brevinin-2 peptides: a Leu/Ala-rich amphipathic helix, alternating hydrophobic and lysine residues, and a C-terminal disulfide ring. These are exactly the features credited in brevinin-2-related peptide literature for activity against MDR A. baumannii. The anionic N-terminal domain appears to be a liability that reduces net cationic charge, dampening membrane affinity. Removal of that domain would be expected to restore the classic brevinin-2 activity profile. The 27-residue truncate would also be shorter than typical AMPs (20-50 residues per manufacturing literature), reducing synthesis cost.
Why it matters
A truncated, high-potency derivative active against MDR A. baumannii would be clinically relevant given the WHO critical-priority status of this pathogen. Validating this would convert a low-activity unusual peptide into a synthetically accessible drug lead, and would establish the anionic domain as a modulatable handle for future engineering.
Plausibility.72
Novelty.33
Impact.73
Basis · grounding1 paper · 2 computed/notes
[1]
paper
Brevinin-2-related peptides and analogs show efficacy against multidrug-resistant A. baumannii, establishing this pathogen as the key benchmark for brevinin-2 activity.
doi: 10.1111/j.1747-0285.2009.00882.x
[2]
sequenceResidues 31-57 SLLGLLKGAGKTLLSAGLNKIACKLTGKC contain lysines at positions 38, 50, 53, 56, and a Leu/Ala-rich hydrophobic face, fully matching the canonical brevinin-2 amphipathic helix and Rana box profile.
[3]
sourceShorter AMPs are preferable for manufacturing cost reduction; a 27-residue truncate would be more economically viable than the 57-residue full-length peptide.
openupdated 2026-06-05

Could the seemingly useless front half of this peptide actually be a built-in safety lock that keeps it dormant until the right environment unlocks it?

Many promising antimicrobial peptides cause side effects by attacking healthy tissue indiscriminately. If this peptide turns out to be activated only by proteases present at an infection site, it could mean a new class of antibiotic that stays inactive in the bloodstream and fires only where bacteria are actually present, which would be a meaningful step toward safer, more targeted treatments.

The hypothesis
The anomalous acidic N-terminal domain (residues 1-30, containing seven Asp/Glu residues: QEDERGADEDDEGEMTEEQK) functions as an autoinhibitory pro-region that suppresses membrane disruption activity until proteolytic cleavage releases the cationic C-terminal effector domain.
Why it’s plausible
Inspection of the sequence reveals a sharply bipartite architecture: residues 1-30 carry a dense cluster of negatively charged residues (net charge strongly negative) immediately followed by a canonical brevinin-2-like amphipathic helix (residues ~31-57, net charge strongly positive, SLLGLLKGAGKTLLSAGLNKIACKLTGKC). This charge imbalance would electrostatically quench interaction of the cationic effector segment with anionic bacterial membranes. Pro-peptide mechanisms of this kind are precedented in defensins and cathelicidins. The low pLDDT in the N-terminal half (overall avg 61.8) is consistent with a disordered or conditionally structured pro-region rather than a folded antimicrobial core.
Why it matters
If the acidic domain is a genuine autoinhibitory pro-segment, the peptide would have a latent, activation-dependent mechanism that explains how it could be stored or circulated without indiscriminate membrane toxicity. This would reframe it as a protease-activated AMP rather than a constitutively active one, with therapeutic implications for context-selective delivery.
Plausibility.64
Novelty.22
Impact.53
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceResidues 1-30: GTISLLCQEDERGADEDDEGEMTEEQKR - contains seven Asp/Glu, strongly anionic; residues 31-57: SLLGLLKGAGKTLLSAGLNKIACKLTGKC - classic amphipathic helix with K34, K38, K50, K53, K56, strongly cationic.
[2]
structureavg_plddt=61.8 and ptm=0.317 indicate a disordered or two-domain structure where one region lacks stable fold, consistent with a flexible pro-region.
[3]
paper
Cationic AMPs require a balance of positive charge and hydrophobicity to interact with negatively charged bacterial membranes; an anionic domain in the same peptide would negate this.
doi: 10.1177/0022034516679973
openupdated 2026-06-05

Does the acidic front section of this peptide electrostatically block its own business end from grabbing onto bacterial membranes, explaining why it performs far worse than close relatives?

Understanding exactly why a peptide underperforms matters because it tells engineers precisely what to fix. If confirmed, this finding would give drug designers a clear map: the structural anchor at the tip (the Rana box) is doing its job, and the problem is the antagonistic front section, meaning targeted edits to that region could convert a weak candidate into a potent one without starting from scratch.

The hypothesis
The C-terminal disulfide-bridged ring (Rana box) in Brevinin-2GHb, formed between C52 and C57 (IACKLTGKC), is necessary for antimicrobial potency but the anionic N-terminal domain reduces the ring's membrane-anchoring efficiency, resulting in an MIC at least 4-fold higher than canonical brevinin-2 family members of similar length.
Why it’s plausible
The Rana box, a disulfide-constrained C-terminal loop, is a defining and functionally important feature of all brevinin peptides: it stabilizes the amphipathic helix and promotes membrane insertion. In Brevinin-2GHb, this ring is likely present (C52-C57 in IACKLTGKC, per sequence). However, the heavily anionic N-terminal extension will create a repulsive electrostatic interaction with the bacterial membrane that must be overcome before the C-terminal helix and Rana box can engage. The prediction's low ptm (0.317) suggests structural coupling between the two halves is poor, further reducing cooperativity. The Rana box is still present and necessary, but it is functionally handicapped.
Why it matters
Confirming this would establish that the Rana box is necessary but not sufficient for high potency in this peptide, and that the anionic domain is the dominant determinant of its (reduced) activity. This directly guides truncation or hybrid design strategies.
Plausibility.37
Novelty.22
Impact.40
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceTwo cysteines at positions 7 (GTISLLC) and 52/57 region (IACKLTGKC); the C-terminal pair is consistent with the Rana box motif seen across all brevinin family members.
[2]
paper
Brevinin-1LTb selectivity and potency are linked to structural features including the Rana box disulfide.
doi: 10.1016/j.peptides.2008.10.016
[3]
structureptm=0.317 (very low) suggests the overall fold is not well-defined as a single unit, consistent with structural discontinuity between anionic N-terminus and the cationic C-terminal helix.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.5581293702125549 boltz-2
3-letter notation
Gly-Thr-Ile-Ser-Leu-Leu-Cys-Gln-Glu-Asp-Glu-Arg-Gly-Ala-Asp-Glu-Asp-Asp-Glu-Gly-Glu-Met-Thr-Glu-Glu-Gln-Lys-Arg-Ser-Leu-Leu-Gly-Leu-Leu-Lys-Gly-Ala-Gly-Lys-Thr-Leu-Leu-Ser-Ala-Gly-Leu-Asn-Lys-Ile-Ala-Cys-Lys-Leu-Thr-Gly-Lys-Cys
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). Brevinin-2GHb antimicrobial peptide (pep-05595, v1). PeptideModel. https://peptidemodel.com/card/pep-05595
@peptide{pep05595,
  sequence = {GTISLLCQEDERGADEDDEGEMTEEQKRSLLGLLKGAGKTLLSAGLNKIACKLTGKC},
  target   = {antimicrobial},
  author   = {peptidemodel},
  year     = {2026},
  status   = {bioassayed}
}
related peptides 5 by signal overlap
references 3 papers
[2] supporting
[3] supporting
discussion no comments
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