Many thanks
Much appreciated
George
Sent from my iPhone
On May 6, 2011, at 16:28, Bill Miller III <brmilleriii.gmail.com> wrote:
> Yes, for #3 you will have to modify (i.e. make new) the protein.prmtop to
> include the water molecule, also, if you are considering the water molecule
> as part of the receptor. So you will need to create/use two new prmtop files
> for this calculation.
>
> -Bill
>
> On Fri, May 6, 2011 at 10:21 AM, George Tzotzos <gtzotzos.me.com> wrote:
>
>> Hi Bill
>>
>> Thank you very much. Indeed I used the original prmtop file. I have now
>> stripped the Na+ ions. So the important thing is the 2nd question.
>>
>> As I mentioned, I've worked out the Delta G of the protein-ligand complex.
>> Given that there's a HOH molecule in the binding site I want to work out its
>> contribution to Delta G binding.
>>
>> For MMPBSA.py, I intend to use
>>
>> 1. complex_solvated.prmtop (original prmtop)
>> 2. complex_HOH.prmtop (modified prmtop)
>> 3. protein.prmtop (original prmtop)
>> 4. ligand.prmtop (original prmtop)
>>
>>
>>
>> For 2 above, my intention is to generate a prmtop file from the a pdb file
>> of the type:
>>
>> ATOM 2206 OXT TYR 141 20.064 34.883 10.511 0.00 0.00
>> TER 0 0
>> ATOM 2207 C1 LIG 142 13.612 30.103 24.510 0.00 0.00
>> TER 0 0
>> ATOM 2254 O WAT 143 13.139 20.066 151.222 0.00 0.00
>>
>> For 3, I though of using the original protein.prmtop but I'm not sure if I
>> have to modify this to include HOH.
>>
>> Am I totally of the mark?
>>
>> Thank you very much for the advice
>>
>> George
>>
>>
>> On May 6, 2011, at 1:38 PM, Bill Miller III wrote:
>>
>>> Your visualization problem appears to be because you are not loading a
>>> corresponding prmtop file with the proper number of atoms. What prmtop
>> did
>>> you use alongside the 2nsHOH.mdcrd? You should be using a prmtop that
>> only
>>> contains the protein, ligand, single water molecule, and 13 Na+ atoms,
>> since
>>> those are the atoms in your mdcrd. It appears as if you are using a
>> prmtop
>>> that contains more than one water molecule. Did you intend to leave the
>> Na+
>>> atoms in the mdcrd? In general, it is not usually advised to use explicit
>>> ions in MM-PBSA calculations. You might want to remove all the sodium
>> ions
>>> from the trajectory prior to running your closest.in file in ptraj.
>>>
>>> To answer your second question, you should be able to use any of the 200
>> pdb
>>> files that were created to generate your new complex/receptor/ligand
>> prmtop
>>> files since the exact coordinates do not matter. Just make sure to divide
>> up
>>> the respective prmtop files exactly as you intend for them to be divided
>>> (i.e. will the water molecule be the ligand? included with the receptor?
>>> included with the small organic molecule as part of the ligand? The
>> answer
>>> to these questions will depend on what question you want to answer by
>>> performing the MM-PBSA calculation).
>>>
>>> I hope that helps.
>>>
>>> -Bill
>>>
>>> On Fri, May 6, 2011 at 6:30 AM, George Tzotzos <gtzotzos.me.com> wrote:
>>>
>>>> Hi everybody,
>>>>
>>>> I'm trying to work out the contribution of a buried water molecule to
>> the
>>>> Delta G of binding of a small organic molecule to a protein of 141
>> residues.
>>>>
>>>> Based on earlier mailings to the list, I tried the following:
>>>>
>>>> 1. A test run to generate pdb files from my 2ns trajectory.
>>>>
>>>> Used: ptraj my.prmtop closest.in
>>>>
>>>> where <closest.in> was
>>>>
>>>> trajin 2ns.mdcrd
>>>> trajout test.pdb pdb
>>>> closest 1 :1-142 first
>>>>
>>>> The output was
>>>> 1> CLOSESTWATERS: saving the 1 closest solvent molecules around atoms
>>>> :1-142
>>>> The current solvent mask is :155-8445
>>>>
>>>>
>>>> PTRAJ: Successfully read in 200 sets and processed 200 sets.
>>>>
>>>> The output was 200 pdb files of the complex with 13 Na+ atoms and one
>> water
>>>> molecule.
>>>>
>>>> 2. Generated the processed trajectory
>>>>
>>>> Used: ptraj my.prmtop process.in
>>>>
>>>> where <process.in> was
>>>>
>>>> trajin 2ns.mdcrd
>>>> trajout 2nsHOH.mdcrd
>>>> closest 1 :1-142 first
>>>>
>>>> The visualisation of the 2nsHOH.mdcrd output is rather weird. I'm
>> attaching
>>>> a snapshot
>>>>
>>>> It shows the closest HOH molecules clustered around the complex and the
>> Na+
>>>> ions localised as a cluster around a specific part of the complex.
>>>>
>>>> I'm pretty sure this is not what I'm supposed to deal with. So there's
>>>> something wrong with the above syntax.
>>>>
>>>> Could anyone please offer some suggestions.
>>>>
>>>> You're help is much appreciated.
>>>>
>>>> And a second related question.
>>>>
>>>> MMPBSA.py will require a new topology file (protein/ligand/water). To
>>>> generate this topology file one would need a starting pdb. Can one use
>> any
>>>> pdb of the 200 generated in step 1 above?
>>>>
>>>> Thanks again
>>>>
>>>> George
>>>>
>>>>
>>>>
>>>>
>>>>
>>>> _______________________________________________
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>>>> http://lists.ambermd.org/mailman/listinfo/amber
>>>>
>>>>
>>>
>>>
>>> --
>>> Bill Miller III
>>> Quantum Theory Project,
>>> University of Florida
>>> Ph.D. Graduate Student
>>> 352-392-6715
>>> _______________________________________________
>>> AMBER mailing list
>>> AMBER.ambermd.org
>>> http://lists.ambermd.org/mailman/listinfo/amber
>>
>>
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>
>
>
> --
> Bill Miller III
> Quantum Theory Project,
> University of Florida
> Ph.D. Graduate Student
> 352-392-6715
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
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Received on Fri May 06 2011 - 08:00:02 PDT
