I am working on MMPs. Before docking the MMPs with a ligand, How to prepare it? What are the conditions/parameters to be decided for ligand preparation? On what basis those conditions are designed ?
Not familiar with MMPs. But I have read Flex manual. It treats water in three ways.
1. remove all the water
2. fix oxygen of water and the hydrogen atoms are flexible to form hydrogen bonds with both ligands and receptors.
3. the program will determine whether the water are essential for the docking according the score function to keep or remove them.
If you have no idea which water should be kept. And MMPs has no similar options like Flex. You'd better try to use Flex. Although it's not free, you can get a trial version for one month.
That will depend on the kind of water molecules. It is generally advised to remove waters prior to docking runs, but if the protein has been reported to have any structural waters, then you will probably need to keep them during docking.
You may keep the so-called structural water molecules. Two kind of rules can be applied to determine which ones are structural. First, a structural water molecule would be reproduced in independent x-ray experiments. Second (if #1 cannot be applied), a water molecule that is deeply buried in a hydrophobic pocket is more likely to be structural.
On the other hand, any kind of water can be dislodged by a ligand, so you can remove them all. You can also run two paralel screenings - with and without structural waters.
Hello Priya,
I am also working on metalloenzymes. I think that you can only decide whether to leave or remove certain water molecules if you try to dock your ligands with different combination of waters. Some water molecules bind in the pocket very strongly, they might be considered as part of the protein. So maybe it is a good idea to keep them during docking if you know which ones are strongly bound. It might be useful to analyze available X-ray structures of your target to get an idea, which waters are conserved. There is also software available that try to predict which molecules feel comfortable in the pocket. On the other hand, there are waters, which can easily migrate in and out of the pocket. Their presence in the pocket might depend on the ligand shape. Sometimes water acts like a bridge between a ligand and certain residue. In this case including water improves the docking pose. However, if the ligand is bulky, including water during docking can prevent it from fitting into the pocket and you might get a false impression about its possible binding mode.
In addition to Dmitri's comment:
If your water molecule makes multiple H-bond interactions, it is most likely to be structural. When considering structural water molecules, first go for those that have 3 or 4 interactions with the protein.
The B-factors for the water molecules can also provide information. If a water molecule is making multiple hydrogen bond interactions, its B-factor will tend to be lower (see for instance Fig 4a in http://www.acsu.buffalo.edu/~sjpark6/archive/Park-PSFB05.pdf). So, you might also compare the B-factor of the water molecule you suspect to be structural with the average B-factor of other water molecules in the structure. That's a relatively quick check.
As long as you do not have relevant indications that a water molecule contributes to the binding of your compound, it is usually better to remove water molecules. This is especially true if you are looking at multiple compound classes. Removing a water that contributes to binding might reduce the accuracy of your docking. But leaving a water molecule right in the middle of where your ligand should be will ruin your docking for sure.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biochemical Techniques
- Analytical Chemistry
- pH