pe
pep-05686 v1 CC-BY-SA-4.0

Beta-defensin 110 antimicrobial peptide

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

statuscomputed targetANTIMICROBIAL length54 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
pTM0.308
avg pLDDT46.7
ranking score0.435
STRUCTURE · PEP-05686 × ANTIMICROBIAL
ranking0.435
?
RECEPTOR UNKNOWN
peptide conformation only · no target structure
target interface 4.5Å peptide drag rotate · ctrl+scroll zoom · right-click pan
sequence54 aa
1510152025303540455054
LLTARKRFPHYGSVDMRR ECAKGNGRCKTECHISEV RIAYCIRPGSLCCLQKYR
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 2026-06-11

Is the disordered region in this peptide actually what makes it effective against many different microbes?

If true, scientists could redesign just the flexible tail to make the peptide more potent or safer, without dismantling the rest of its structure. This would speed up antibiotic development by giving engineers a clear target region to modify.

The hypothesis
Beta-defensin 110 adopts a canonical beta-defensin fold stabilized by three disulfide bonds (C20-C31, C27-C47, C40-C48 or an equivalent pairing), and the low pLDDT of 46.7 reflects intrinsic disorder in the N-terminal cationic tail (residues 1-19) rather than absence of a folded core, meaning the tail can sample multiple conformations that broaden its membrane-targeting range.
Why it’s plausible
Six cysteines at positions 20, 27, 31, 40, 47, 48 match the beta-defensin C-C-C spacing. pLDDT below 50 for a 54-residue peptide with six cysteines is most consistent with a disordered N-terminal tail preceding a structured disulfide-bonded beta-sheet core, a feature documented in other beta-defensins where tail flexibility correlates with broader spectrum activity.
Why it matters
If the low-confidence prediction reflects tail disorder rather than global misfolding, the peptide retains a functional defensin scaffold and the tail can be re-engineered independently to tune potency without disrupting the disulfide core.
Plausibility.78
Novelty.55
Impact.60
Basis · grounding2 computed/notes
[1]
sequenceSix cysteines at positions 20, 27, 31, 40, 47, 48 consistent with three canonical beta-defensin disulfide bonds; N-terminal stretch LLTARKRFPHYG (res 1-12) is cationic and flexible.
[2]
structurepLDDT=46.7 on a 54-residue monomer; low global score on a known disulfide-rich fold class is consistent with disordered tail pulling the mean down, not whole-structure disorder.
openupdated 2026-06-11

Could changing a structural weak point in this peptide let it stay active inside the protective slime that bacteria use to resist treatment?

Bacterial biofilms protect many chronic infections, from wound infections to implant-associated infections, and are notoriously hard to treat. A version of this peptide engineered to stay active inside biofilms could give doctors a new option for patients whose infections keep coming back.

The hypothesis
Replacing the CC doublet at positions 47-48 of beta-defensin 110 with a single Cys and a non-cysteine hydrophobic residue would redirect disulfide pairing into a non-canonical three-disulfide topology that is more resistant to the reductive environments of biofilm matrices, increasing antibiofilm potency without changing the overall fold.
Why it’s plausible
Adjacent cysteines (C47-C48) are unusual in beta-defensins; they create a local strain point and are vulnerable to reductive glutathione in biofilm microenvironments. Spacing them apart or removing one forces alternative disulfide topology. Defensins with altered disulfide connectivity have shown enhanced stability in reducing conditions, as demonstrated in engineered theta-defensin analogs.
Why it matters
Biofilm infections are a leading cause of chronic antibiotic failure in veterinary and human medicine. A defensin engineered for reductive stability could maintain activity inside biofilms where current AMPs lose function.
Plausibility.62
Novelty.68
Impact.62
Basis · grounding1 paper · 1 computed/note
[1]
sequenceC47 and C48 are adjacent in the sequence PGSLCC, an atypical CC doublet for beta-defensins; adjacent Cys pairs introduce local conformational strain and a single-reduction vulnerable bond.
[2]
paper
Review positions defensins and AMPs as alternatives to conventional antibiotics in veterinary medicine, with stability in infection microenvironments being a key translational challenge.
doi: 10.1038/s41573-019-0058-8
openupdated 2026-06-11

Does this peptide automatically become stronger at the acidic pH of an infected wound or inflamed tissue?

If the peptide activates itself at the acidic conditions found inside infected tissue, it could kill bacteria where they live while sparing healthy tissue nearby. For patients, this would mean a more targeted antibiotic with fewer side effects.

The hypothesis
The dense cationic charge in the N-terminal segment (positions 1-7: LLTARKR, net +4) combined with the hydrophobic core around residues 8-16 (FPHYGSVDM) creates a selectivity gradient that favors binding bacterial membranes (high phosphatidylglycerol) over mammalian membranes (high phosphatidylcholine), giving a therapeutic window that widens at slightly acidic pH where His10 becomes protonated (+1 extra charge).
Why it’s plausible
His10 (H10) in the motif RFPHY has a pKa near 6.5. At pH 5.5-6.5 (infected tissue, lysosomes), protonation adds a positive charge, enhancing electrostatic attraction to anionic bacterial membranes while mammalian membrane selectivity is less pH-sensitive.
Why it matters
A built-in pH-responsive charge switch would make the peptide self-activating in infected tissue, reducing systemic toxicity risk, a key bottleneck for clinical translation of AMPs.
Plausibility.70
Novelty.50
Impact.62
Basis · grounding1 paper · 1 computed/note
[1]
sequenceH at position 10 in RFPHYG; clustered R5-K6-R7 give baseline +4 at neutral pH; His protonation at acidic pH adds one more positive charge selectively at infection sites.
[2]
paper
Review discusses AMP membrane selectivity mechanisms and efflux resistance, noting surface-activity screening context for AMPs.
doi: 10.1177/0022034516679973
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.4351818561553955 boltz-2
3-letter notation
Leu-Leu-Thr-Ala-Arg-Lys-Arg-Phe-Pro-His-Tyr-Gly-Ser-Val-Asp-Met-Arg-Arg-Glu-Cys-Ala-Lys-Gly-Asn-Gly-Arg-Cys-Lys-Thr-Glu-Cys-His-Ile-Ser-Glu-Val-Arg-Ile-Ala-Tyr-Cys-Ile-Arg-Pro-Gly-Ser-Leu-Cys-Cys-Leu-Gln-Lys-Tyr-Arg
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). Beta-defensin 110 antimicrobial peptide (pep-05686, v1). PeptideModel. https://peptidemodel.com/card/pep-05686
@peptide{pep05686,
  sequence = {LLTARKRFPHYGSVDMRRECAKGNGRCKTECHISEVRIAYCIRPGSLCCLQKYR},
  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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