This repository tracks a curated library of designed peptides intended to:
- compete for Cu(II) (Cu sequestration away from Aβ)
- modulate Aβ conformational equilibria, with special interest in shifting populations away from β-prone states and toward α-helical character when possible.
The library is organized for high interpretability: clean baselines, clamp variants, and mechanistic controls.
consideration.md— source-of-truth human document:- complete peptide list, ordered by family → length
- design rationale per family
- peptide-specific notes and caveats
CBP_mapping.csv— machine-readable index:- CBP name ↔ legacy IDs ↔ sequence ↔ length ↔ family ↔ role
If you only read one file, read
consideration.md.
Peptides are named using the convention:
CBP{GreekLetter}{index}
- The Greek letter encodes the design family.
- The index increases with peptide length within that family (short → long).
This is deliberate: it makes it easy to compare within-family length effects and avoids mixing fundamentally different design levers.
Exact membership is defined in consideration.md.
-
Family α — ATCUN baselines
Minimal-confounder Cu(II) capture designs (DAH/GGH heads), no internal clamp. -
Family β — ATCUN + internal HxxxH clamp
Cu(II) capture plus an embedded i,i+4 His clamp (e.g., HAAAH/HRAAH/HQAAH) for helix locking / secondary metal-contact patch. -
Family γ — ATCUN-dead controls (N-acetylated)
Same scaffold/clamp features, but N-acetylation disables ATCUN-like binding to isolate mechanism. -
Family δ — Charged interaction comparators
Higher electrostatic encounter rate with Aβ (use as “stress tests” and interpret only relative to α/β baselines).
For each peptide (apo and Cu-bound) and for competition systems (Aβ + Cu + peptide), the recommended minimum is:
- Helicity (DSSP) — time series + per-residue helix propensity
- Cu coordination stability — Cu–donor distances, coordination numbers, geometry metrics
- Cu exposure — SASA around Cu center (reactivity proxy)
- Aβ–peptide contacts — contact maps + residence times
- Self-association — peptide–peptide contacts (especially for long/charged constructs)
- If feasible: Cu transfer thermodynamics (ΔG_exchange) for
Aβ–Cu + peptide → Aβ + peptide–Cu
- N-acetylated (γ-family) peptides are required to separate “ATCUN Cu capture” from “scaffold/clamp binding”.
- Always benchmark interaction-prone peptides (δ-family) against α/β families before interpreting any “α-induction” effects.
This repository is the main hub of the CBP project (library + mapping tables). The four family-specific repositories below contain the corresponding structural ensembles.
Reference conditions (unless otherwise stated): PEP-FOLD4, pH 7.5, ionic strength 10 mM.
-
CBP_alphas → https://github.com/pepmirko/CBP_alphas
PEP-FOLD4 computed structures for the alpha family. -
CBP_betas → https://github.com/pepmirko/CBP_betas
PEP-FOLD4 computed structures for the beta family. -
CBP_gammas → https://github.com/pepmirko/CBP_gammas
PEP-FOLD4 computed structures for the gamma family. -
CBP_deltas → https://github.com/pepmirko/CBP_deltas
PEP-FOLD4 computed structures for the delta family.
Rule 1 — Update the machine index first
Add new entries to CBP_mapping.csv (or your upstream CSV if you regenerate it), including:
- sequence (with
Ac-prefix if N-acetylated), - intended role,
- family assignment rationale.
Rule 2 — Then update consideration.md
- ensure the peptide appears in the correct family,
- keep length ordering within family,
- add a short peptide-specific note if it introduces a new lever.
Rule 3 — Avoid premature complexity
- Prefer canonical amino acids first.
- Introduce non-canonical caps/staples only after the baseline mechanism is demonstrated.
If this library is used in a manuscript or report, please cite the relevant primary literature motivating:
- ATCUN-like Cu(II) binding motifs,
- i,i+4 metal-assisted helix stabilization,
- helix capping strategies,
- and metal-triggered helix nucleation concepts (where applicable).
(Repository-specific citation guidance can be added here once finalized.)