I want to connect proteins together to form a dimer. As seen in the picture, the monomers come close to each other along the edge of the higher-order structure (forget about the sulfate there). How can I find out, where I need to introduce an Xaa->Cys mutation so that the most stable disulfide bond is formed between the proteins? It is easy to get a visual clue where about a mutation might be good, but is there a good computational method to calculate the energies and scan through some possibilities?

(I would also go with hydrophobic or van de Waals interactions. Basically, I just want to glue those proteins together.)

Edge of two proteins (modelled in Chimera)


If you have a structural model for the interaction, i.e. atomic coordinates, then you could use our software called Disulfide by Design. See the following links.



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    $\begingroup$ Perhaps you could give an overview of how the program works and what it is useful for. At the moment this seems rather like spam. $\endgroup$ – bon Oct 20 '15 at 16:05
  • $\begingroup$ I don't think it looks like spam. Actually, it's rather interesting. But so far it seems that I can only calculate energy minima of residues that are in the same protein, not in multiple ones ...? $\endgroup$ – ste Oct 20 '15 at 20:25
  • $\begingroup$ Far from spam. I am the author of the software and publications. The original algorithm has been used in more than 90 published research papers, including a number in Cell, Science, and Nature. The above link to the paper in biomedcentral describes the software. You can find additional information on the underlying algorithm in my original paper here: bioinformatics.oxfordjournals.org/content/19/14/1852.full.pdf $\endgroup$ – user22106 Oct 22 '15 at 13:15
  • $\begingroup$ Also . . . the software has been used in several studies that linked separate proteins or subunits. Here are the PubMed IDs for a few examples: 18583346, 19425108, 24315638. The energy calculated in DbD is associated only with the actual bond. It is a relative value used for selecting bonds most likely to form. $\endgroup$ – user22106 Oct 22 '15 at 13:35
  • $\begingroup$ You might find useful our recent review article on disulfide engineering: sciencedirect.com/science/article/pii/S0014579313008685 $\endgroup$ – user22106 Oct 22 '15 at 13:51

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