program for flexible protein complex system

Linear (OLIGOMER), and non-linear (MIXTURE) analysis, singular value decomposition (SVDPLOT), addition of missing fragments (BUNCH, CORAL), analysis of flexible systems (EOM/RANCH & GAJOE), flexible refinement of high-resolution models (SREFLEX)
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sevny
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Joined: 2011.12.15 19:33

program for flexible protein complex system

#1 Post by sevny » 2013.03.13 21:48

Hi All,

I am wondering if there is a program can be used for dealing with flexible protein complex system with multiple subunits, each subunit has multiple domains linked by flexible liners. I was trying with EOM, but had problems. I am not sure if it is correct, but seems that the EOM is more suitable for a single chain or oligmers with symmetry. For a heterodimer, it may work if the C-terminus of one subunit is spacially close to the N-terminus of the other subunit; otherwise the results are not good. Another question is, For a multiple domain protein run with EOM, when using crystal structures of the domains, which contain gaps in the crystal structures because of flexible loops, one has to split the pdb files into pieces to avoid the gaps. However, for the following case, I had difficulty making it working. For a two-domain protein (domain A and B), there is a linker between A and B, A binds B moderately with some flexibility, crystal structures of A and B are available, but both have gaps in the pdb files. So I had to split A and B into A1, A2, A3 and A4, and B1 and B2, seperately. When running EOM, I need to fix the relative positions of A1, A2, A3 and A4, also, the relative position of B1 and B2, but wanted to have A and B moving as rigid entities, respectively. Is this possbile with EOM? Thanks a lot in advance for your comments.

regards,

Steve

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Giancarlo
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Location: EMBL Hamburg, Germany

Re: program for flexible protein complex system

#2 Post by Giancarlo » 2013.03.15 17:55

sevny wrote:I am wondering if there is a program can be used for dealing with flexible protein complex system with multiple subunits, each subunit has multiple domains linked by flexible liners. I was trying with EOM, but had problems. I am not sure if it is correct, but seems that the EOM is more suitable for a single chain or oligmers with symmetry. For a heterodimer, it may work if the C-terminus of one subunit is spacially close to the N-terminus of the other subunit; otherwise the results are not good.
With EOM 2.0 you can do that. I do not get what you mean with the case you mentioned.
sevny wrote:Another question is, For a multiple domain protein run with EOM, when using crystal structures of the domains, which contain gaps in the crystal structures because of flexible loops, one has to split the pdb files into pieces to avoid the gaps. However, for the following case, I had difficulty making it working. For a two-domain protein (domain A and B), there is a linker between A and B, A binds B moderately with some flexibility, crystal structures of A and B are available, but both have gaps in the pdb files. So I had to split A and B into A1, A2, A3 and A4, and B1 and B2, seperately. When running EOM, I need to fix the relative positions of A1, A2, A3 and A4, also, the relative position of B1 and B2, but wanted to have A and B moving as rigid entities, respectively. Is this possbile with EOM? Thanks a lot in advance for your comments.
If there are gaps in the crystal you need to fix the domains in the original position and reconstruct the missing parts. But this does not allow you to make the entire domains flexible at the same moment.
What you might do is:

1) Make the missing gaps in the single domain A and B
2) Use them as crystals and allow them to be flexible

At a resolution of SAXS should not be a problem if the reconstructed gap (A1-A2,A2-A3, etc.) are not atomically perfect.

Hope this can help you.

Ciao,
Giancarlo

sevny
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Posts: 8
Joined: 2011.12.15 19:33

Re: program for flexible protein complex system

#3 Post by sevny » 2013.03.15 23:58

Hi Giancarlo,

Thank you so much for your reply. I really appreciate it.



With EOM 2.0 you can do that. I do not get what you mean with the case you mentioned. (sorry, I do not know how to quote, so copy and paste :) )


For my case, the protein complex is a heterodimer with two subunits M and N. M has 2 domains, M1 and M2; N has N1, N2 and N3. While M1 and N1 form a complex, other domains may have some flexibility, meaning M2, N2 and N3 may have different orientations within limited space. If I use EOM to get an ensemble, how to input the sequence file for EOM? From my understanding, the sequence used in EOM should be a single chain (I could be wrong). For my case, I have two different chains, if I input them sequentially in a file, that means to connect the chains together, which is incorrect.

Thanks a lot,

Regards,
Steve

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