Hi Armando,

Have you looked at predicted models e.g. Alphafold for the full-length protein?

+ Are there experimentally determined structures for full length structural 
homologues or orthologues from other species to validate computational models?

You may be able to align your domains against the full length that way and 
add-in the Alphafold model of the linker to generate a complete structure

If there is significant contact surface between the two domains, then you may 
need to do some molecular dynamics to resolve clashes / create optimal 
inter-domain contacts – again the predicted model and / or homologous 
experimentally determined structures may help with seeing which bits ae likely 
to have conformational change in the complete structure vs the individual 
domain structures.

Cheers, Charlie.


From: CCP4 bulletin board <[email protected]> On Behalf Of Armando Albert
Sent: 26 July 2023 09:14
To: [email protected]
Subject: [ccp4bb] On the production of a two domain protein

WARNING: This message was sent by an external party. Report suspicious messages 
via the “Report Phishing” button in Outlook.

Dear all,
We are trying to characterize a protein consisting of two domains. We have 
successfully produced, purified and crystallized both domains independently. 
However, we are unable to overexposes a soluble form of the full-length 
protein. Can anyone provide a strategy to merge back the independent domains 
into a single protein chain or to modify the construct to succeed in the 
overproduction of the full-length protein?
Armando

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