pe
pep-05499 v1 CC-BY-SA-4.0

Mauriporin antimicrobial peptide

A peptide that kills or slows the growth of harmful microbes; 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
pTM0.341
avg pLDDT56.2
ranking score0.518
STRUCTURE · PEP-05499 × ANTIMICROBIAL
ranking0.518
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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
MLIVDEVNSSRFGGFFRRIW KSKLAKRLRSKGKELLKDYA NRVINGGPEEEAAGPPARK
in the news 6 articles
Hypotheses5 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 latch onto a specific part of the bacterial outer shell before punching through it, rather than just sticking by static charge?

If the FGGFF motif really does grip the bacterial surface first, researchers could design shorter, cheaper peptides that do two jobs at once: kill bacteria AND neutralize the toxic debris they release when they die. That matters most for treating severe infections where the dying bacteria themselves can trigger dangerous immune overreactions.

The hypothesis
The FGGFF aromatic cluster in mauriporin's central region binds the lipid A headgroup of Gram-negative bacterial lipopolysaccharide (LPS) through pi-stacking and hydrophobic contacts, and this LPS interaction is a prerequisite for subsequent outer-membrane disruption rather than a direct consequence of bulk electrostatic attraction.
Why it’s plausible
The sequence contains FGGFF (positions approximately 12-16), an aromatic-rich motif flanked by two arginines (FGGFFRR). Phenylalanine-rich motifs are documented as LPS-binding modules in other AMPs and in endotoxin-neutralizing peptides. The GG dipeptide within this motif provides a flexible hinge that could allow the two Phe residues to adopt a clamp geometry around the glucosamine-phosphate moiety of lipid A. The adjacent RR provides electrostatic anchoring to the phosphate groups. This is structurally distinct from the canonical helix-driven membrane disruption.
Why it matters
If FGGFF is the primary LPS recognition element, truncation studies removing this motif would quantitatively separate LPS-neutralizing from direct membrane-lytic activity, opening a path to dual-function antiendotoxin-antimicrobial derivatives.
Plausibility.62
Novelty.52
Impact.60
Basis · grounding1 paper · 1 computed/note
[1]
sequenceFGGFFRR motif centered around positions 12-18; double-Gly provides conformational flexibility and double-Phe provides aromatic contacts; flanking RR provides electrostatic anchoring.
[2]
paper
Non-receptor-mediated membrane permeabilization is a hallmark of AMPs; however, LPS recognition upstream of lysis is a distinct mechanism documented for some cationic peptides.
doi: 10.1128/aac.01341-13
openupdated 2026-06-05

Could the acidic ends of this peptide act like a safety lock, keeping it folded and harmless until it reaches bacteria?

If the peptide really does switch on only near bacteria, it could explain why it works against multiple bug types without causing widespread harm to the body. This kind of built-in selectivity, if confirmed, could guide engineers toward next-generation antibiotics that are less toxic and less likely to cause side effects.

The hypothesis
Mauriporin disrupts bacterial membranes through a two-step mechanism in which the acidic flanking regions (N-terminal MLIVDEVNSS and C-terminal PEEEAAGPPARK) act as electrostatic gatekeepers that suppress self-aggregation at physiological pH, while the central cationic-hydrophobic core (FGGFFRRIWKSKLAKRLRSK) drives membrane insertion and pore formation upon contact with the anionic bacterial surface.
Why it’s plausible
The sequence contains a striking bipolar charge distribution: acidic residues (D7, E8, E52, E53, E54) flank a strongly cationic-hydrophobic core. This architecture is unusual for canonical AMPs, which are uniformly cationic. The acidic flanks could suppress inter-peptide aggregation in solution, releasing the active core only on the negatively charged bacterial membrane. The low avg_plddt (56.2) is consistent with a disordered free form that undergoes a disorder-to-helix transition on membrane contact, a mechanism documented for other AMPs.
Why it matters
If the flanking acidic regions function as built-in solubility and selectivity modulators, this would explain mauriporin's reported multifunctional activity and could guide engineering of next-generation AMPs with reduced systemic toxicity by exploiting the same gating logic.
Plausibility.52
Novelty.43
Impact.58
Basis · grounding1 paper · 2 computed/notes
[1]
sequenceAcidic N-terminus MLIVDEVNSS (D5, E6) and C-terminal PEEEAAGPPARK (E50, E51, E52) flank the cationic-hydrophobic core FGGFFRRIWKSKLAKRLRSK.
[2]
structureavg_plddt 56.2 for the free monomer indicates intrinsic disorder, consistent with a disorder-to-structure transition upon membrane binding.
[3]
paper
Cationic AMPs adopt amphipathic conformations upon membrane contact; disordered free forms are common.
doi: 10.1177/0022034516679973
openupdated 2026-06-05

Does this peptide attack drug-resistant bacteria in a different way than colistin, bypassing the shield those bacteria built up?

Colistin-resistant Acinetobacter baumannii is on the WHO's most-dangerous-pathogens list, and doctors are nearly out of options for it. If mauriporin attacks this bacteria through a different route, it could become a treatment option for patients who have no other choices, particularly in intensive care settings.

The hypothesis
Mauriporin retains bactericidal activity against multidrug-resistant Acinetobacter baumannii strains that are resistant to colistin through outer-membrane modifications, because mauriporin's mode of entry is independent of the lipid A phosphoethanolamine modification that abrogates colistin binding.
Why it’s plausible
An axis_hit reference explicitly names mauriporin in the context of antibiofilm and antimicrobial activity against multidrug-resistant A. baumannii. Colistin resistance in A. baumannii arises primarily from addition of phosphoethanolamine or galactosamine to lipid A, which reduces the net negative charge of the outer membrane and blocks colistin. Mauriporin's unusually large size (59 aa) and mixed acidic-cationic character could allow it to engage with membrane components beyond lipid A, such as outer membrane proteins or lipoproteins, circumventing the colistin-resistance modification.
Why it matters
Colistin-resistant A. baumannii represents a critical WHO-priority pathogen with very limited treatment options. A peptide with confirmed anti-A. baumannii activity that bypasses colistin-resistance mechanisms would have direct clinical relevance.
Plausibility.38
Novelty.43
Impact.77
Basis · grounding1 paper · 1 computed/note
[1]
paper
Reference chunk explicitly cites 'Almaaytah A, Tarazi S... Antimicrobial and antibiofilm activity of mauriporin, a multifunc...' in the context of multidrug-resistant A. baumannii.
doi: 10.2147/idr.s199473
[2]
sequenceAt 59 residues, mauriporin is larger than most AMPs and has an unusual acidic-cationic charge distribution that could engage outer membrane components beyond the lipid A target of colistin.
openupdated 2026-06-05

Does this peptide stay folded and inactive in the bloodstream, then unfold and activate in the saltier environment of an infection site?

If confirmed, this would mean the peptide is naturally tuned to activate right where infection is happening and stay quiet elsewhere in the body. That kind of built-in geographic targeting could reduce side effects and might eventually allow doctors to fine-tune formulations for specific types of infections.

The hypothesis
The PEEEAAGPPARK C-terminal segment forms an intramolecular salt bridge with the cationic core under low-ionic-strength conditions, auto-inhibiting membrane insertion; physiological ionic strength (150 mM NaCl) disrupts this bridge and liberates the hydrophobic core for membrane engagement.
Why it’s plausible
The sequence contains a strongly cationic central region (RRIWKSKLAKRLRSK, net charge approx. +8) followed by a C-terminal EEE run (net charge -3 to -3). At low ionic strength, Coulombic attraction between these regions could create a compact, auto-inhibited conformation. At physiological ionic strength, counterion shielding would relax this constraint, consistent with observed salt-dependent activity changes reported for related AMPs. The AA and PP residues flanking EEE introduce rigidity that would make this salt-bridge-dependent conformation structurally defined.
Why it matters
Salt-dependent conformational switching would mean mauriporin activity is modulated by local ionic conditions, such as those at infected tissue surfaces versus bloodstream, providing an intrinsic selectivity mechanism and a target for ionic-strength-tuned formulations.
Plausibility.43
Novelty.52
Impact.52
Basis · grounding2 computed/notes
[1]
sequenceCentral RRIWKSKLAKRLRSK (highly cationic) and C-terminal PEEEAAGPPARK (acidic EEE flanked by rigid PP and AA motifs) are positioned to form intramolecular electrostatic contacts.
[2]
structureLow avg_plddt (56.2) in monomer prediction is consistent with a conformationally heterogeneous free form rather than a stably folded structure, supporting the idea of environment-dependent folding.
openupdated 2026-06-05

If we cut off the floppy ends of this peptide, would the remaining core last longer without being digested and still work just as well?

Most peptide drugs get chewed up by the body's own enzymes before they reach an infection. If trimming this peptide down to its active core makes it more resistant to that breakdown, it could be a more practical drug candidate, cheaper to manufacture and more effective in the bloodstream, which are two of the biggest hurdles for turning any peptide into a real medicine.

The hypothesis
Truncation of mauriporin to its cationic-hydrophobic core (approximately residues 12-40, spanning FGGFFRRIWKSKLAKRLRSK) will retain or exceed full-length antibacterial potency while significantly reducing the proteolytic susceptibility contributed by the flexible, unstructured N-terminal (MLIVDEVNSS) and C-terminal (PEEEAAGPPARK) tails.
Why it’s plausible
The axis_hits show that trypsin sensitivity is a key limitation for AMP therapeutics, and multiple references describe rational truncation to improve proteolytic stability. The N-terminal MLIVDEVNSS and C-terminal PEEEAAGPPARK regions contain multiple trypsin cleavage sites (R, K) and are low-plddt (disordered) regions that likely contribute to protease exposure. The central core contains the canonical amphipathic elements. Removing the flanking tails reduces the number of exposed cleavage sites and may increase the helical propensity of the core by removing the competing disorder.
Why it matters
A shorter, protease-resistant core variant would substantially improve the therapeutic index and reduce manufacturing cost (fewer residues), addressing two major barriers to AMP clinical translation identified in the bundle.
Plausibility.52
Novelty.23
Impact.57
Basis · grounding2 papers · 1 computed/note
[1]
paper
Trypsin sensitivity dramatically reduces AMP antimicrobial activity; protease-resistant truncated variants are a validated engineering strategy.
doi: 10.1016/j.ejps.2021.105784
[2]
paper
High manufacturing cost ($100-600/gram) makes shorter peptide variants with equivalent potency economically critical.
doi: 10.1038/nbt1267
[3]
sequenceResidues 12-40 contain the FGGFFRR aromatic block and the IWKSKLAKRLRSK cationic helix-forming segment; flanking regions are compositionally distinct and likely dispensable for membrane activity.
details expand to inspect
full evidence table1 metrics
metricvaluetool
ranking score 0.5176429748535156 boltz-2
3-letter notation
Met-Leu-Ile-Val-Asp-Glu-Val-Asn-Ser-Ser-Arg-Phe-Gly-Gly-Phe-Phe-Arg-Arg-Ile-Trp-Lys-Ser-Lys-Leu-Ala-Lys-Arg-Leu-Arg-Ser-Lys-Gly-Lys-Glu-Leu-Leu-Lys-Asp-Tyr-Ala-Asn-Arg-Val-Ile-Asn-Gly-Gly-Pro-Glu-Glu-Glu-Ala-Ala-Gly-Pro-Pro-Ala-Arg-Lys
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). Mauriporin antimicrobial peptide (pep-05499, v1). PeptideModel. https://peptidemodel.com/card/pep-05499
@peptide{pep05499,
  sequence = {MLIVDEVNSSRFGGFFRRIWKSKLAKRLRSKGKELLKDYANRVINGGPEEEAAGPPARK},
  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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