Jason, thanks a lot ! Your detailed explanation made me more understand what to take precautions in the designed methodology.
Statistical sampling is the next issue to tackle here. Without the water calculation in mmpbsa, I took 5000 snapshots as input. Now, adding water for calculation choosing particularly only buried waters, steps 1b & 1c below cant be done manually if 5000 frames are to be taken. I am not expert in writing scripts.
Suggestions please .....
Amor
--- On Wed, 25/8/10, Jason Swails <jason.swails.gmail.com> wrote:
From: Jason Swails <jason.swails.gmail.com>
Subject: Re: [AMBER] Water deeply buried for MMPBSA calculations
To: "AMBER Mailing List" <amber.ambermd.org>
Date: Wednesday, 25 August, 2010, 7:19 PM
Hello,
On Wed, Aug 25, 2010 at 6:54 AM, Amor San Juan <amorsanjuan.yahoo.com>wrote:
> Moving on towards another level ....
>
> Recently, I tackled a simple approach of choosing closest waters for
> mmpbsa. Now, I aim to put ONLY buried water molecules into mmpbsa
> calculations. I am aware that in MD it is not the same water molecule in
> every frame. Is my goal possible to achieve ?
>
This sounds like the "closest" command that you've been asking about
before. One thing you have to make sure of, though, is that you keep the
SAME number of water molecules in each frame. MM/PBSA will not be able to
take into account a variable number of water molecules in each frame.
>
> To my knowledge, the program NACCESS can identify buried water and it
> requires PDB as input. On the other hand, MMPBSA requires a trajectory as
> input. Clearly, I have to set-up a strategy to satisfy each programs.
>
> I thought of strategy by "unbuilding" followed by "rebuilding" of
> trajectory.
>
> ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
> Step-1: Unbuilding trajectory
>
> 1a. Take snapshots from input trajectory and convert to its corresponding
> pdb file
>
Ptraj can do this quite easily.
> 1b. Using the pdb output from 1a, use naccess program to identify buried
> water
> 1c. Remove the non-buried water
>
Again, ptraj can do this if naccess can't.
>
> Step-2: Rebuilding trajectory
>
> Combine all trajectories. Make a corresponding topology and feed into
> mmpbsa for binding energy calculations.
>
ptraj can do this as well. Just trajin the PDB files.
> ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
>
> Input trajectory for step-1a contains bulk TIP3P waters. To do preliminary
> filtering for input in step-1a, two ptraj options are available:
>
> OPTION-1 Use closest command to select 10 water molecules at nearest
> distance to ligand. Output expected is solute (protein+ligand) and solvent
> (10 water). This output will be used as input trajectory for step-1a.
>
This is your best option.
>
> OPTION-2 Use strip command to strip all atoms further than 3 angstroms of
> ligand. Output of number of selected water will vary in each frame, and this
> could cause problem when this input goes through rebuilding stage of
> trajectory.
>
If there are a different number of water molecules each frame, then a
*single* topology file will not work for every frame (since each frame could
have a different number of atoms/water molecules. This case will not work
for MM/PBSA. Moreover, it doesn't make sense to compare an energy with 10
water molecules to an energy with 20 water molecules.
Hope this helps,
Jason
>
> Bottomline, it is easy to unbuild the trajectory but the challenge lies on
> rebuilding it.
>
>
> I hope to receive feedback from the forum.Thanks.
>
>
>
> Amor
>
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> http://lists.ambermd.org/mailman/listinfo/amber
>
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Graduate Student
352-392-4032
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Received on Thu Aug 26 2010 - 04:30:03 PDT
