Multichain Comparative Modeling

Modeller Comparative is an interface to Modeller for comparative (“homology”) modeling of proteins and protein complexes.

The example shows modeling the human (shades of blue) from the mouse (brown and tan) complex of programmed death-1 (PD-1) with its ligand PD-L2, PDB 3bp5.

Comparative modeling requires a template structure and a target-template sequence alignment for each unique chain. The sequences of human PD-1 and PD-L2 targets were fetched from UniProt and associated with the corresponding chains in the template structure, see model-pdl-setup.cxc. (Pairwise or multiple sequence alignments could have been used, but in this case, the template structure was simply associated with the target sequence.) Sequence-structure association shows mismatches in the Sequence Viewer: pink boxes for sequence differences between mouse and human, and gray outlines around the parts missing from the structure.

Three models were made with with default settings (other than the number of models), and the best-scoring model is shown. Two positions where sequence differences change the interfacial H-bonds are displayed.

G-Protein Switch Regions

The GDP- and GTP-bound conformations of the transducin α-subunit (1tag and 1tnd, respectively) differ primarily in three regions, termed switch 1, switch 2, and switch 3. The structures have been superimposed with matchmaker and shown as cartoons, with “empty” outlines where the structures are almost the same (for simplicity, only one conformation's outlines are shown). The GTP analog GTPγS is displayed as spheres color-coded by heteroatom. For 2D labels and image setup other than structure orientation, see the command file switch.cxc.

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