Protein modelling of genes carrying mutations/deletions

Question

[Deep Adhya]

Dear Biostar community,

Is there any way to model a truncated protein with missing amino acid sequences (as a result of genomic deletions in exons) in-silico? If so, does anyone know of reliable web tools or software for this purpose? I would also be grateful, if anyone can direct me to published articles if any of this kind of work?

Thank you

Best wishes, Deep Adhya

[Kevin Blighe]

I would originally suggest the tools listed at the Protein Model Portal, but I now see that the group no longer has funding. However, they still provide links to certain websites where you can upload any protein sequence and have it modeled.

Kevin

Answer 1

[Mensur Dlakic]

The answer to your question depends on your exact circumstances. If you have a homologous template, then the answer is yes. By this I mean that if there is a crystal structure of a similar protein that includes the part missing in yours, you will be able to model the deleted part. If there is no homologous structure, you will still be able to model it, but not in a reliable way. I suggest you check the links on the right side of this page and previous discussions here and here.

[Deep Adhya]

Thanks Mensur. My aim is to model a protein (eg NRXN1) without the deleted amino acid sequence of interest. I have found a couple of ab-initio protein modellers, the I-TASSER and Phyre2, and they appear to model the wild-type sequences quite accurately. I will try out the protein sequence with the delete sequences now, but there would be no way of knowing if they have been modelled reasonably accurately? Thanks