Modeling a Homodimer using a Monomers Created in HM (video)
Last Updated: Jul 25, 2018 09:45AM PDT
This is a basic method for any oligomer. More complex protocols with more automation may also be introduced, but this is a generally applicable method that allows you flexibility, assuming that when you look at step (I.1) the homologs do not extensively interpenetrate but are separate globular proteins.
NOTE: This workflow will also work for multi-chain Homology Modeling. For step II, find a template where there's a homologous structure of something else binding to your protein of interest. Once you find this template, continue with this workflow, using this template in the place of 2Q8S.
Example for a C2 Symmetric Homodimer (Hamster PPAR)
I. Predict Monomer Structure
1. Paste target monomer sequence (e.g. Hamster PPAR) in Cyrus HM and run Homology Modeling
2. Download PDB of top resulting model (Monomer Model)
II. Find Homodimer Template
3. Run blastp on target sequence (e.g. HamsterPPAR) against the PDB
4. Based on your specific knowledge and literature, select the most relevant homodimer PDB structure as a template for dimerization (e.g. 2Q8S human PPAR complex)
a. Download 2Q8S PDB and reserve for later
b. Method requires a template with your desired symmetry
III. Pre-Symmetrize Model
5. In PyMOL, superimpose Monomer Model to Chain A of template 2Q8S and an identical copy of Monomer Model to Chain B of template 2Q8S
6. Save each of the aligned Monomer Models from PyMOL to two separate PDBs
7. Using a text editor, combine the two PDBs with a TER line in between, and by changing Chain identifier from A to B in one of the monomers. This is the Pre-Symmetrized Model
IV. Optimize Side Chains
8. Load the Pre-Symmetrized Model into Cyrus CAD. This needs side chains fixed
9. Run Relax or Repack with five or more repetitions to optimize side chains. This places side chains realistically.
10. Select structure with lowest energy. This is your final Homodimer Model!
While this method is used for a C2 symmetric homodimer in the example above, it can also be used to template oligomeric models off of any template regardless of symmetry.