ArchCandy-2.0 program detects amyloid-forming regions in protein sequences.


Download ArchCandy-1.0

The core structural element of a majority of naturally-occurring and disease-related amyloid fibrils is a β-arcade representing a parallel and in register stacks of β-strand-loop-β-strand motifs called β-arches (reviewed in Kajava et al. FASEB J. 2010 24:1311). "ArchCandy" was developed based on an assumption that protein sequences that are able to form β-arcades are amyloidogenic.

This program allows :
-to distinguish between amyloidogenic and non-amyloidogenic sequences
-to localize the amyloidogenic regions within the protein
-to predict the 3D structures of amyloid fibrils.

Please, cite:
Ahmed A.B., Znassi N., Château M.T. and Kajava A.V. A structure-based approach to predict predisposition to amyloidosis. (2015) A lzheimers & Dementia 11(6):681-690. 10.1016/j.jalz.2014.06.007 .
Falgarone T., Villain E., Guettaf A., Leclercq J., Kajava A.V. TAPASS: Tool for annotation of protein amyloidogenicity in the context of other structural states (2022) J Struct Biol. 214(1):107840. doi:10.1016/j.jsb.2022.107840.

Paste one protein sequence in FASTA format (Example):

NOTE : Maximum 15000 characters

Options


Score Threshold

Transmembrane Helix filter

ArchCandy-2.0 - Documentation


  • 1. Input
    •
    • 1.1 Format
    • 1.2 Score Threshold
    • 1.3 "Transmembrane Helix Filter" option
  • 2. Output
    •
    • 2.1 Cumulative Score
    • 2.2 Highest Score
    • 2.3 SeqView
    • 2.4 Table

1. Input format


1.1 Format

Amino acid sequence in FASTA format.


1.2 Score Threshold

Each predicted amyloidogenic region has a score. The “Score Threshold” option allows the user to output only those predictions that are higher than the specified score value. Our benchmark of datasets with soluble proteins and with proteins known to form amyloids suggested that the ArchCandy prediction of the amyloidogenicity is non-significant if the score is below 0.40, it is ambiguous if the score is between 0.40 and 0.57 and significant for the score over 0.57. The default value of the web-version (recommended to distinguish between amyloidogenic and non-amyloidogenic sequences) is 0.40.


1.3 "Transmembrane Helix Filter" option

As transmembrane (TM) regions are located in the membranes in the alpha-helical conformation, it is unlikely that they will form amyloid fibrils. Therefore, if this option is activated, predictions are not made in these regions.


2. Output

2.1 Cumulative Score
It is the sum of the scores of all amyloidogenic candidates at a given amino acid position. If a query sequence has signal peptide (SP), transmembrane helix region (TM) or unstructured region (UN), their regions are shown by rectangles.

2.2 Highest Score
It is the highest scores among all amyloidogenic candidates at a given amino acid position. The maximal possible value is 1.0.

2.3 SeqView
It shows location of the amyloidogenic regions within the protein. Ranges of the scores are shown by a colour code. To zoom a region (especially if a query protein is so long that the amino acid sequence is not visible), it is necessary to point the cursor onto the sequence (a cross sign will appear), to press the left button of the mouse moving the cursor. To come back to the original size, click on the right button of the mouse.

2.4 Table
Table contains 2D diagrams of the predicted beta-arches, followed by type of arc conformation coded as in Hennetin et al., 2006, doi: 10.1016/j.jmb.2006.02.039. The N-terminus of the arch is located at the right-bottom.