Waltz, AlphaFold and ESMfold Predictions on a Human Prion Protein Tiled Peptide Library Highlight a C-Terminal Region with Strong Conformational Sensitivity
Grant, J. E.; Vranicar, S. J.
Show abstract
Short, linear sequence motifs within the human prion protein (PrP) may encode local aggregation tendencies that are not apparent from full-length sequence analysis. To map intrinsic amyloidogenic potential across PrP, we generated a complete one-residue-step library of overlapping 15-mer peptides from the 253-residue human PrP sequence and evaluated each peptide using WALTZ in both high-specificity and best-overall-performance modes, with full-length SNPeffect4/WALTZ output used for comparison. Peptide-level WALTZ analysis identified several candidate amyloidogenic regions, including an N-terminal signal-peptide segment spanning approximately residues 8-21/22 that was not detected in the publicly available full-length WALTZ/SNPeffect4 output. Predictions made using AlphaFold 3.0 also identified a short C-terminal area whose representative peptides formed either -helix or pair of {beta}-strands, indicating a region of potential higher susceptibility to conformational dynamics. This computational study supports the use of peptide tiling as a complementary screening strategy for identifying candidate short aggregation-prone motifs in PrP and other misfolding-associated proteins.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies 94%
- Prion propagation is dependent on key amino acids in Charge cluster 2 within the prion protein 91%
- Intrinsically disordered protein ensembles shape evolutionary rates revealing conformational patterns 91%
Similar papers in this journal
Similar papers in this journal
- Peptides derived from gp43, the most antigenic protein from Paracoccidioides brasiliensis, form amyloid fibrils in vitro: implications for vaccine development 93%
- PACT - Prediction of Amyloid Cross-interaction by Threading 93%
- Increased Dynamics of α-Synuclein Fibrils by β-Synuclein Leads to Reduced Seeding and Cytotoxicity 92%
Similar papers in this journal
Similar papers in this journal
- Antibodies raised against a structurally defined Aβ oligomer mimic protect human iPSC neurons from Aβ toxicity at sub-stoichiometric concentrations 91%
- The RNA encoding the microtubule-associated protein tau has extensive structure that affects its biology 91%
- scFv intrabody targeting wildtype TDP-43 presents protective effects in a cellular model of TDP-43 proteinopathy 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.