The LYRA server predicts structures for either T-Cell Receptors (TCR) or B-Cell Receptors (BCR) using homology modelling. Framework templates are selected based on BLOSUM score, and complementary determining regions (CDR) are then selected if needed based on a canonical structure model and grafted onto the framework templates. The final output is a complete three-dimensional model of the target antibody that can be downloaded or displayed on-line.

First, input a pair of TCR or BCR protein sequences in any order. The sequences should either be entered directly into the text area field labeled "Enter protein sequence(s)”, or can be taken from a file that has to be uploaded using the "Browse" button. The sequences can be supplied in two different formats:

• One continuous sequence
• FASTA format

The input sequence will be interpreted as FASTA if an opening ">" character is found, or as a continuous sequence otherwise.
All sequences have to be amino acids specified in single letter code
(ACDEFGHIKLMNPQRSTVWY)

Advanced options consist of options to select different side chain modeling methods. It also provides option to blacklisting any template(s) for modeling.

This one is easy. Click the submit button, and a result screen similar to the one below should appear.

The Summary table shows template structures and calculated canonical structures for both chains.

Canonical Structures(CS)
Shown below is the definitions of the canonical structures for TCR chains. Structures are predicted using the affinity propagation algoritm, and the exemplars are shown as being the representative PDB structure.

Loop Loop Length Canonical Structure Representative PDB Any Any 0 Unable to determine CS A1 8 1 2VLR 9 2 3QFJ 3 3TJH 4 3ARB 5 4G8E 10 6 4OZH 7 4JRX A2 5 1 3QIU 2 4OZG 6 3 4L3E 7 4 4P23 5 3MV8 6 3REV 7 3SCM 8 8 4G9F A3 9 1 3SKN 10 2 3QEQ 11 3 4L4V 4 4P46 12 5 3PL6 6 3QFJ 13 7 3TF7 14 8 3HUJ 9 3MV8 10 2BNQ 15 11 4P4K 12 1MI5

Loop Loop Length Canonical Structure Representative PDB Any Any 0 Unable to determine CS B1 9 1 3QEU 2 4MAY 10 3 3O6F 4 4JFF B2 16 None 17 1 4JFH 18 2 2IAL 3 3MV8 19 4 4MAY 5 3QIU 6 1KB5 20 7 3O6F B3 Any 0 B3 loops are scored/grafted solely on BLOSUM62 score.

BCR Canonical structures are predicted using sequence-based rules. The rules are described in the following table:

Loop Loop Length Canonical Structure Constraints Any Any 0 Unable to determine CS H1 6 4 7 1 8 2 9 3 H2 3 1 71:AVL 2 71:RK 4 3 71:AVL 4 71:RK 6 5 71:AVL 6 71:RK H3 3 1 4 3 94:ACDEFGHILMNPQSTVYW 4 94:RK 5 6 94:ACDEFGHILMNPQSTVYW 7 94:RK 6 9 94:ACDEFGHILMNPQSTVYW 10 94:RK 7 12 94:ACDEFGHILMNPQSTVYW 13 94:RK 8 15 94:ACDEFGHILMNPQSTVYW 16 94:RK 9 18 94:ACDEFGHILMNPQSTVYW 19 94:RK 10 21 94:ACDEFGHILMNPQSTVYW 22 94:RK 11 24 94:ACDEFGHILMNPQSTVYW 25 94:RK 12 27 94:ACDEFGHILMNPQSTVYW 28 94:RK 13 30 94:ACDEFGHILMNPQSTVYW 31 94:RK 14 33 94:ACDEFGHILMNPQSTVYW 34 94:RK 15 36 94:ACDEFGHILMNPQSTVYW 37 94:RK 16 39 94:ACDEFGHILMNPQSTVYW 40 94:RK 17 42 94:ACDEFGHILMNPQSTVYW 43 94:RK 18 45 94:ACDEFGHILMNPQSTVYW 46 94:RK 19 48 94:ACDEFGHILMNPQSTVYW 49 94:RK 20 51 94:ACDEFGHILMNPQSTVYW 52 94:RK

Loop Loop Length Canonical Structure Constraints Any Any 0 Unable to determine CS K1 6 1 29:VIL 7 2 29:VIL 8 6 29:VIL 11 5 29:VIL 12 4 29:VIL 13 3 29:VIL K2 3 1 K3 4 4 90:Q 5 3 96:P 90:Q 6 90:Q 94:L 6 1 95:P 90:HNQ 2 90:Q 94:P 7 5 95A:P 90:Q

Loop Loop Length Canonical Structure Constraints Any Any 0 Unable to determine CS L1 7 7 28:VIL 66:N 8 8 9 1 25:G 5 25:R 28:G 10 2 25:G 66:K 90:S 31:FHY 3 66:L 90:L 6 25:G 66:K 90:S 31:ND L2 3 1 L3 6 1 7 3 92:D 95:ST 4 95:CVPILDNHFYWMEQKRAG 8 2

Alignment: The sequences are aligned with the input sequence, the template sequence and the variable loops.

Modeled Structure is displayed using JSmol Viewer (JavaScript-Based Molecular Viewer From Jmol).
It allows the user to display or hide both chains and to highlight each loop.

Click on Download button to download the model generated by LYRA.

The downloaded model file can be visualized locally using Jmol viewer. Jmol is a free, open source molecule viewer that is cross-platform. Instructions on how to download, install and run the viewer can be found here.