pe
pep-05516 v1 CC-BY-SA-4.0

Beta-defensin 113 germ-killing peptide

A naturally occurring peptide that kills or slows harmful bacteria; used only as a lab research tool.

statuscomputed targetANTIMICROBIAL length59 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
pTM0.260
avg pLDDT51.9
ranking score0.467
STRUCTURE · PEP-05516 × ANTIMICROBIAL
ranking0.467
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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
sequence59 aa
151015202530354045505559
GPSVSQKKTKEDAGRKRECY LVRGACKSSCNSWEYIYNYC STEPCCVVREYQKPVSKSI
in the news 6 articles
Hypotheses6 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

If we snip off part of the peptide, does it still work against bacteria?

If the killing power lives in the compact, folded core of this molecule, researchers could strip away the extra tail and make a shorter, cheaper version that survives longer in the body. That would bring a potential antibiotic treatment closer to practical use.

The hypothesis
The antimicrobial activity of beta-defensin 113 is primarily mediated by membrane disruption via the C-terminal amphipathic core (residues 19-46, containing the disulfide-stabilized beta-sheet) rather than by the flexible cationic N-terminal tail, and consequently persists even when the N-terminal tail is cleaved.
Why it’s plausible
The sequence shows two structurally distinct regions: a disordered cationic N-terminus (GPSVSQKKTKEDAGRKRE, aa 1-18) and a disulfide-rich C-terminal core (C19-C26-C30-C40-C45-C46) that forms the canonical beta-defensin triple-stranded beta-sheet. The axis_hits literature documents that some beta-defensin activities persist after linearization or fragmentation, and that the disulfide-stabilized fold confers proteolytic stability. If the killing activity resides in the folded core, N-terminal truncation variants would retain potency while gaining serum stability.
Why it matters
Identifying the minimal killing domain guides rational truncation engineering to produce a shorter, cheaper-to-synthesize, more protease-resistant therapeutic lead from this 59-aa peptide.
Plausibility.79
Novelty.38
Impact.73
Basis · grounding2 papers · 1 computed/note
[1]
sequenceSix cysteines at positions 19, 26, 30, 40, 45, 46 define the canonical beta-defensin C1-C5, C2-C4, C3-C6 disulfide topology; aa 1-18 lack cysteines and are likely unstructured.
[2]
paper
Activities of beta-defensins persist even when peptides are linearized, fragmented, or structures otherwise altered, suggesting activity is not wholly disulfide-dependent but raises the question of which domain carries killing.
doi: 10.1042/bj20082242
[3]
paper
Linear peptides are more susceptible to protease degradation than defensins stabilized by disulfide bridges, implying the folded core region confers resistance.
doi: 10.1186/s12866-018-1190-z
openupdated 2026-06-05

Could this peptide act as a signal that calls immune cells to the site of infection?

Some related peptides are known to summon immune cells by docking onto receptors on their surface. If beta-defensin 113 does the same, it could be useful beyond fighting bacteria, possibly as a component in vaccines or treatments for inflammatory conditions.

The hypothesis
Beta-defensin 113 binds CCR2 or CCR6 on dendritic cells and T cells through its cationic N-terminal tail (KKTKEDAGRK, residues 7-16), triggering chemotactic signaling analogous to human beta-defensins 2 and 3.
Why it’s plausible
Human beta-defensins 2 and 3 are known chemokine-receptor ligands: hBD-2 signals through CCR6 and hBD-3 through CCR2 and CCR6. The N-terminal region of beta-defensin 113 carries a dense cluster of basic residues (K7, K8, K10, R15, K16, R17) that structurally mirrors the cationic receptor-engagement domain conserved across the hBD family. The card annotates no target (null), yet the peptide retains the full beta-defensin scaffold. If this chemotactic activity is real, it would be a non-antimicrobial function currently unrecognized for this specific defensin.
Why it matters
Establishing CCR2/CCR6 binding would reframe beta-defensin 113 as an immunomodulatory peptide, not merely a bactericidal one, opening therapeutic angles in inflammatory recruitment and vaccine adjuvancy.
Plausibility.53
Novelty.63
Impact.75
Basis · grounding2 papers · 1 computed/note
[1]
sequenceResidues 7-17 contain five basic side-chains (K7, K8, K10, R15, K16, R17) forming a cationic patch consistent with chemokine-receptor engagement.
[2]
paper
Broad immunomodulatory activities of beta-defensins are noted as difficult to correlate with specific structural features; CCR interactions are a known class mechanism.
doi: 10.1042/bj20082242
[3]
paper
Host-defense peptides have non-antimicrobial roles in innate signaling that are underexplored for individual family members.
doi: 10.1038/s41573-019-0058-8
openupdated 2026-06-05

Does one specific building block determine how deeply the peptide buries itself in a bacterial membrane?

If a single amino acid controls how well the peptide locks onto and disrupts bacterial membranes, swapping it out in the lab becomes a precise dial for tuning potency. That could speed up the design of more effective, targeted versions of the molecule.

The hypothesis
The tryptophan residue at position 33 (within the WEYIYNY motif) is a critical determinant of beta-defensin 113 membrane insertion depth and thus antimicrobial potency, because indole side-chains partition preferentially at the lipid-water interface and anchor the peptide in a membrane-active orientation.
Why it’s plausible
Inspection of the sequence reveals a central aromatic-rich stretch W33-E34-Y35-I36-Y37-N38-Y39-C40 containing one tryptophan and three tyrosines. Tryptophan is known to position itself at the glycerol-water interface of phospholipid bilayers and is over-represented in membrane-active peptides. For a beta-defensin, whose disulfide core organizes a rigid scaffold, the tryptophan at this position could act as a membrane-depth anchor that orientates the entire beta-sheet for optimal pore formation or carpet-model disruption. Substituting W33 with a non-aromatic residue of similar bulk should selectively abolish membrane disruption without eliminating structural fold.
Why it matters
Pinpointing W33 as a potency determinant provides a single-residue engineering handle: conservative replacement tests the mechanism, and non-natural indole analogs could tune membrane partition coefficients for pathogen-specific targeting.
Plausibility.62
Novelty.58
Impact.57
Basis · grounding2 papers · 1 computed/note
[1]
sequenceW33 sits within the loop connecting beta-strands of the defensin core (WEYIYNY, residues 33-39), flanked by aromatic residues and preceding cysteine C40.
[2]
paper
Difficulty correlating structural features with biological activities of beta-defensins underscores why residue-level determinants like W33 remain uncharacterized for most family members.
doi: 10.1042/bj20082242
[3]
paper
No single mechanistic model adequately explains defensin effectiveness in vivo, and membrane-insertion depth is a candidate explanatory variable.
doi: 10.1016/j.jip.2018.07.005
openupdated 2026-06-05

Could this peptide, applied directly in the mouth, kill the bacteria that cause gum disease and tooth decay?

Gum disease affects hundreds of millions of people and existing treatments are limited. A peptide that can be applied directly in the mouth sidesteps the biggest hurdle for peptide medicines, getting them through the gut and bloodstream, which could make a real therapy feasible sooner.

The hypothesis
Beta-defensin 113 exerts activity against oral biofilm-forming bacteria (including Streptococcus mutans and Porphyromonas gingivalis) at concentrations achievable in the oral cavity, making it a candidate for topical periodontal or anti-caries therapy.
Why it’s plausible
One reference DOI (10.1177/0022034516679973) is explicitly from the Journal of Dental Research, and its text references AMPs in an oral/dental context. Beta-defensins are constitutively expressed in oral epithelium and are part of the innate oral immune barrier. Beta-defensin 113 carries the same structural hallmarks (cationic, amphipathic, disulfide-stabilized) as oral beta-defensins that have established activity against oral pathogens. Because the oral cavity is a topical compartment, systemic bioavailability barriers (a major limitation for AMP therapeutics per the oral-bioavailability axis hits) are irrelevant, making this one of the most tractable clinical translation routes for this peptide class.
Why it matters
Topical oral delivery bypasses the central pharmacokinetic obstacle for peptide drugs, and periodontal disease is a high-prevalence condition with inadequate antimicrobial options; demonstrating efficacy here would provide a direct translational path.
Plausibility.58
Novelty.50
Impact.58
Basis · grounding2 papers · 1 computed/note
[1]
paper
Reference is from the Journal of Dental Research (ISSN 0022-0345), contextualizing AMP resistance mechanisms within oral/dental research, consistent with oral defensin biology.
doi: 10.1177/0022034516679973
[2]
paper
Oral administration challenges for peptide drugs highlight the contrast: topical oral use avoids GI degradation entirely, making beta-defensin 113 more viable via this route.
doi: 10.1039/d5ra03731j
[3]
sequenceThe six-cysteine motif and cationic profile are shared with hBD-1, hBD-2, and hBD-3, which have documented activity against oral pathogens including Streptococcus and Fusobacterium.
openupdated 2026-06-05

Could this peptide attack cancer cells while leaving healthy cells alone?

Some cancer cells display a chemical flag on their surface that healthy cells keep hidden, and this peptide is naturally attracted to that flag. If that selectivity holds up in testing, it could point toward a new type of cancer treatment for blood cancers or skin cancers that works differently from standard chemotherapy.

The hypothesis
Beta-defensin 113 is cytotoxic to cancer cells with elevated phosphatidylserine surface exposure (e.g., certain leukemia and melanoma lines) at concentrations non-toxic to normal human cells, owing to the same electrostatic selectivity mechanism that governs its antimicrobial action.
Why it’s plausible
The literature in the selectivity axis explicitly states that cancer cells lose membrane lipid asymmetry, exposing phosphatidylserine on the outer leaflet, which renders them electrostatically negative and susceptible to cationic AMPs. Beta-defensin 113 carries a high cationic charge density: counting K and R residues across the sequence (K7, K8, K10, K16, R15, R17, K23 approximating RGAC region, R49 area) gives a strongly positive net charge at physiological pH. This is the same charge profile responsible for bacterial selectivity over mammalian cells. Cancer selectivity through this route is a non-obvious extension.
Why it matters
If validated, beta-defensin 113 could seed an oncology program targeting liquid tumors or surface-accessible solid tumors, distinct from its antibacterial application and avoiding the resistance mechanisms relevant to antibiotics.
Plausibility.52
Novelty.42
Impact.65
Basis · grounding2 papers · 1 computed/note
[1]
paper
Cancer cells lose membrane asymmetry, making their exterior more negatively charged, which may explain why some cationic peptides selectively target them over normal eukaryotic cells.
doi: 10.1177/0022034516679973
[2]
sequenceThe peptide contains at minimum seven cationic residues (K, R) in a 59-aa sequence, conferring a strongly positive charge suited to electrostatic targeting of negatively charged membranes.
[3]
paper
Structure-activity relationships linking cationic character to selectivity between bacteria and host cells are noted as a key but incompletely understood feature of beta-defensins.
doi: 10.1042/bj20082242
openupdated 2026-06-05

Could a peptide known for killing bacteria also disable viruses like flu or coronaviruses?

Viruses with a lipid outer coat share a weakness with bacteria: their surface carries a negative charge that positively charged peptides can disrupt. If beta-defensin 113 works against these coated viruses, and if viruses cannot easily mutate their way around membrane-based attacks, it could become a durable broad-spectrum antiviral that stays effective even as viruses evolve.

The hypothesis
Beta-defensin 113 inhibits enveloped viruses (such as SARS-CoV-2 or herpes simplex virus) by directly disrupting the viral lipid envelope, independent of any host receptor interaction, because the same amphipathic cationic scaffold that kills bacteria can intercalate into viral membranes.
Why it’s plausible
Multiple human beta-defensins (hBD-1, hBD-2, hBD-3) have documented antiviral activity against enveloped viruses including HIV, influenza, and coronaviruses. The axis_hits literature (10.1073/pnas.1817376116) cites Wilson et al. on antiviral mechanisms of human defensins. Beta-defensin 113 shares the canonical six-cysteine fold with all antiviral beta-defensins. Viral envelopes are compositionally analogous to bacterial outer membranes in possessing a net-negative surface charge accessible to cationic peptides. The peptide currently has no antiviral tag or target annotation, so this activity would be a new recognized function.
Why it matters
Antiviral defensins that act on the lipid envelope have a high barrier to viral resistance (membrane composition is host-derived and cannot easily mutate), making beta-defensin 113 a potentially durable broad-spectrum antiviral scaffold if this activity is confirmed.
Plausibility.48
Novelty.45
Impact.65
Basis · grounding2 papers · 1 computed/note
[1]
paper
Reference cites Wilson et al. (2013) on antiviral mechanisms of human defensins, situating beta-defensin family members in antiviral innate immunity.
doi: 10.1073/pnas.1817376116
[2]
sequenceThe six-cysteine canonical fold and net-positive charge at physiological pH are shared features of hBD-1 and hBD-3, which have demonstrated anti-HIV and anti-influenza activities.
[3]
paper
Distinct biological activities of beta-defensins remain incompletely mapped to structural features, implying antiviral function may exist in beta-defensin 113 but has not been attributed.
doi: 10.1042/bj20082242
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.4669721722602844 boltz-2
3-letter notation
Gly-Pro-Ser-Val-Ser-Gln-Lys-Lys-Thr-Lys-Glu-Asp-Ala-Gly-Arg-Lys-Arg-Glu-Cys-Tyr-Leu-Val-Arg-Gly-Ala-Cys-Lys-Ser-Ser-Cys-Asn-Ser-Trp-Glu-Tyr-Ile-Tyr-Asn-Tyr-Cys-Ser-Thr-Glu-Pro-Cys-Cys-Val-Val-Arg-Glu-Tyr-Gln-Lys-Pro-Val-Ser-Lys-Ser-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). Beta-defensin 113 germ-killing peptide (pep-05516, v1). PeptideModel. https://peptidemodel.com/card/pep-05516
@peptide{pep05516,
  sequence = {GPSVSQKKTKEDAGRKRECYLVRGACKSSCNSWEYIYNYCSTEPCCVVREYQKPVSKSI},
  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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