constructing a modified sugar

[subramanian]

Friends,
i want to incorporate a modified sugar into a canonical DNA duplex. Basically i am interested in incorporating a locked nucleic acid sugar, where the 2' oxygen and 4' carbon of the sugar has a methylene linkage. Such a structure is available in pdb:2X2Q. i would like to know the possibility of using 3DNA for replacing the normal sugar with such modified sugar in a DNA duplex.

Thanks,
Subbu

[xiangjun]

Hi Subbu,

Thanks for posting this question. While I understand what you mean, I must say that 3DNA (in its current version) does not have direct means to get the job done. I may be able to come up with a solution after reading the publication associated with PDB id 2X2Q, check the PDB coordinates of the entry, and then play around with 3DNA to fit the bill. Obviously, this will take time.

To make this effort worthwhile, I'd ask you to perform a survey of other tools, e.g., UCSF Chimera, PyMol etc, to see if they already provide similar functionality. Of course, others viewers of this thread are more than welcome to jump in with their opinions. Hopefully, more users will get actively participated in such discussions that will help shape further development of 3DNA.

Xiang-Jun

[subramanian]

Xiang-Jun,
I extracted chain A and B from the 2X2Q pdb, changed the residue names to A, T, G, and C instead of what is there in original pdb. I tried to run find_pair and analyze and i am able to get the output. So i guess i wont have a problem in analyzing such sugar modified DNA.

Just for curiosity, I looked in the fiber/str04 where there is a A.pdb, I guess this is the template Adenine structure used for building a fiber model with -4 option. I extracted the co-ordinates of just one sugar locked Adenine from the pdb and replaced A.pdb file. It has two extra atoms (O2' and C6') as compared to the standard Adenine. I then tried to constructed just a A:T base pair but i didnt find any change in the sugar, the result was a standard sugar.

I guess some more thing should be necessary. I read the discussion titled 'helical Parameters of a Modified nucleic acids' in the forum. What i understood was that they have tried analyzing a modified base by adding new residue names in baselist.dat and also Atomic_?.pdb files. Am i supposed to do a similar additions ?.

Cheers,
Bala

[subramanian]

Dear Xiang-Jun,
Just want to update you that as of now, i am successful in making the modification using chimera software which has a menu called 'Build structure'. It would be nice to have this feature incorporated in 3DNA.

[xiangjun]

...i am successful in making the modification using chimera software which has a menu called 'Build structure'. It would be nice to have this feature incorporated in 3DNA.

Glad to hear that you are successful in making sugar modification with Chimera 'Build structure'. If that does a decent job, why should 3DNA bother to compete (recreating the wheel)? That's exactly why I asked you the question in my preview reply.

Xiang-Jun

[mauricio esguerra]

Hi,

If what you want is to make your nucleic acid with some favorite step parameters and then modify the sugars to LNA, then I suggest using Accelerys Discovery Studio 3.1 Visualizer (ADS), which is free for academics.
That is, you make the non-LNA in 3DNA, and then you open it with ADS which allows you to modify the sugars an leave everything else intact.
It's also nice if you wanna do MD runs with CHARMM, since it allows you to save in crd and psf format which CHARMM needs to run.

Cheers,

M.