Dear Soumendranath,

Please see the attached file. I have copied the paper's title and abstract for quick view.

Rapid and Accurate Prediction and Scoring of Water Molecules in Protein Binding Sites

Gregory A. Ross, Garrett M. Morris, Philip C. Biggin

Published: March 1, 2012DOI: 10.1371/journal.pone.0032036

Abstract

Water plays a critical role in ligand-protein interactions. However, it is still challenging to predict accurately not only where water molecules prefer to bind, but also which of those water molecules might be displaceable. The latter is often seen as a route to optimizing affinity of potential drug candidates. Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set. In addition, we combined data-mining, heuristic and machine learning techniques to develop probabilistic water molecule classifiers. When applied to WaterDock predictions in the Astex Diverse Set of protein ligand complexes, we could identify whether a water molecule was conserved or displaced to an accuracy of 75%. A second model predicted whether water molecules were displaced by polar groups or by non-polar groups to an accuracy of 80%. These results should prove useful for anyone wishing to undertake rational design of new compounds where the displacement of water molecules is being considered as a route to improved affinity.

Hoping this will be helpful,

Rafik

Thanks for your answer Rafik but I want to know some sort of tool or programme which can calculate the presence of no. water molecules as a function of time in a particular binding site/cavity during molecular dynamics simulation

Dear Soumendranath,

"Is there any software or programme which can calculate the number of water molecules present in the active site of protein or within a host-guest system during a explicit solvent molecular dynamics simulation". This is the question.

"Using a protocol we call WaterDock, we show that the freely available AutoDock Vina tool can be used to predict accurately the binding sites of water molecules. WaterDock was validated using data from X-ray crystallography, neutron diffraction and molecular dynamics simulations and correctly predicted 97% of the water molecules in the test set:". This is the answer.

Rafik

Hi Rafik, I don't need a docking engine. I want some programme which can calculate the occupancy of water molecules in a particular binding site as a function of time.

Dear 

To my knowledge, the number of water molecules found in any active site is less than four molecules. Therefore, there is no need to look for a program for counting this tiny amount.

Rafik

Hey there, 

Things you should do:

1) Familiarize yourself with VMD's interface (5-10 mkinutes)

2) Familiarize yourself with script usage in VMD's TCL engine (5-10 minutes)

3) Familiarize yourself with the way the system is set up in your case. (1 minute)

4) Familiarize yourself with the use of atomselect language (if you do the above - 5minutes)

5) Put together a small script (5-10 lines depending on how you code) (5-10 minutes)

6) Run the code.

7) get the answer.

steps 1-5 :: 15-20 minutes.

steps 6: depends on your system's trajectory.

step 7: depends on if you did what you think you did.

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Explanation:

In case you are not interested doing all this on your own, here is what you need.

In a TCL script define a selection (e.g 5Ang volume around a certain group of residues that make your binding site) --- Within this selection count waters. 

The above should give you one number say 13. 

If you load a trajectory from a simulation and loop the code over all frames in the trajectory you will have a time series, with 1 number for each frame indicating the number of water molecules counted in your volume of interest. You can change the 5A area to be 10 or whatever - depending what your neighboring threshold is.

Hope this helps.

Best,

/A

p.s. VMD is a free tool you can download from the groups website. Learning it now will help you a lot in manipulating your data instead of looking around for help. Of course there are a tonne of other things but I find this most convenient. If you are stuck somewhere -- drop me a message and I will see what I can do ...

Good luck. 

In my experience, module watershell from cpptraj (AMBER package programme) could be one interesting option. You can monitor water (and any other solvent) in PDB files or coordinated ones. This option is also available for MD simulations as well. The key point, is selection of the corresponding amino acid (or group of amino acids) that you want as center of your shell and the radio of them.

https://amberhub.chpc.utah.edu/watershell/

I hope this works for you.

Best regards, Bruno.