Is it possible to do Molecular Replacement for synthesized "small" molecule X-ray data?
Hi PHENIX users, We've got a synthesized molecule, called Cucurbit[7]uril, molecular weight 1163 Da. We were able to grow crystals of cucurbit[7]uril with one of its ligand. This crystal diffracted to 1.5A at our X-ray machine. The dilemma is that, at this resolution, we can't use small molecule crystallography softwares to solve the structure (correct me if I'm wrong, we need at least 1A resolution?), while macromolecular X-ray softwares are really not designed for synthesized molecules. We have collected diffraction data of this crystal with decent quality. So I'm wondering if there's any way we can put a known crystal structure of cucurbit[7]uril and solve the structure of the complex. We have tried AutoMR but the solution is not very encouraging. Any suggestion will be gratefully appreciated. Best, -- Yi(Yves) Wang Department of Biochemistry Structural Biology & Biophysics Program Duke University BS: University of Science and Technology of China School of Life Sciences, National Laboratory for Physical Sciences at Microscale Tel: +1-919-236-3307 (Cell) +1-919-684-0235 (Lab 1) +1-919-660-1634 (Lab 2) Office: A20 LSRC / 5301 FFSC E-Mail: [email protected] Mail: Box 90317, Chemistry Department
Dear Yves, That's probably getting close to the limit of the ratio of the size of the molecule to the resolution, which is one of the main things determining whether molecular replacement will work. At 1.5A, you'd have to have a pretty accurate model of the structure as well (i.e. RMSD signficantly under 1A, at a guess). Another problem with molecular replacement for small molecules is that small molecule crystals tend to be tightly packed, which makes things somewhat harder. Nonetheless, I've done test calculations in the past that show it can work. One thing you should watch out for: Phaser only accepts atoms that are given as ATOM records in a PDB file, so if you have HETATM records, those atoms will be rejected. If you'd like to send the logfile from Phaser (preferably off-line), I could take a look at it. Regards, Randy Read On Dec 8 2009, Yves Wang wrote:
Hi PHENIX users,
We've got a synthesized molecule, called Cucurbit[7]uril, molecular weight 1163 Da. We were able to grow crystals of cucurbit[7]uril with one of its ligand. This crystal diffracted to 1.5A at our X-ray machine. The dilemma is that, at this resolution, we can't use small molecule crystallography softwares to solve the structure (correct me if I'm wrong, we need at least 1A resolution?), while macromolecular X-ray softwares are really not designed for synthesized molecules.
We have collected diffraction data of this crystal with decent quality. So I'm wondering if there's any way we can put a known crystal structure of cucurbit[7]uril and solve the structure of the complex. We have tried AutoMR but the solution is not very encouraging.
Any suggestion will be gratefully appreciated.
Best,
What a nice molecule according to http://en.wikipedia.org/wiki/Cucurbituril ... Did you by any chance crystallize it as a salt? In the previous century, this happened to me with a cyclodextrin complex that had a Br atom. The Br was visible in the native patterson, and that had at the time triggered my interest in 'ARP' that was soon after to become 'ARP/wARP'. If there is a chance for a 'heavy' atom there, use it! Looking at the molecule I would expect a cloud of solutions in MR, all pretty good but every ~50 degrees on gamma, given the cyclic molecule, if I got the structure right. So, you would have no 'unique' solution. However, putting any of the top solutions in 'ARP/wARP map improvement by free atoms addition and deletion' should/could yield a good map with 1.5 A data. Apologies for the non-phenix shameless self-promoting plugin, but I think you might find this actually useful. Tassos On 8 Dec 2009, at 21:18, Randy J. Read wrote:
Dear Yves,
That's probably getting close to the limit of the ratio of the size of the molecule to the resolution, which is one of the main things determining whether molecular replacement will work. At 1.5A, you'd have to have a pretty accurate model of the structure as well (i.e. RMSD signficantly under 1A, at a guess). Another problem with molecular replacement for small molecules is that small molecule crystals tend to be tightly packed, which makes things somewhat harder. Nonetheless, I've done test calculations in the past that show it can work.
One thing you should watch out for: Phaser only accepts atoms that are given as ATOM records in a PDB file, so if you have HETATM records, those atoms will be rejected.
If you'd like to send the logfile from Phaser (preferably off-line), I could take a look at it.
Regards,
Randy Read
On Dec 8 2009, Yves Wang wrote:
Hi PHENIX users,
We've got a synthesized molecule, called Cucurbit[7]uril, molecular weight 1163 Da. We were able to grow crystals of cucurbit[7]uril with one of its ligand. This crystal diffracted to 1.5A at our X-ray machine. The dilemma is that, at this resolution, we can't use small molecule crystallography softwares to solve the structure (correct me if I'm wrong, we need at least 1A resolution?), while macromolecular X-ray softwares are really not designed for synthesized molecules.
We have collected diffraction data of this crystal with decent quality. So I'm wondering if there's any way we can put a known crystal structure of cucurbit[7]uril and solve the structure of the complex. We have tried AutoMR but the solution is not very encouraging.
Any suggestion will be gratefully appreciated.
Best,
_______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb
participants (3)
-
Anastassis Perrakis
-
Randy J. Read
-
Yves Wang