AMBER Archive (2005)

Subject: Re: AMBER: Re: TI tutorial

From: Jiten (jiten_at_postech.ac.kr)
Date: Tue Jun 28 2005 - 11:36:59 CDT

Dear D. A. Case,

Thanks for your mail. As I mentioned in my second mail - I apply the changes
on the PERT.charges system. Could you slightly clarify my understanding for
TI calculation taking my example at hand.

I have two protein systems bound with the same drug molecule. In one
position at the active site of the protein ALA --> GLY are mutated which
makes a free energy loss for ~ 1 kcal/mole. I wish to find out this
difference using the TI calculations. (It works well with MM-PBSA method,
therefore it should give better result with free energy calculations
considering explicit solvents)

I can have two approach for this. Please let me know if I am still sounding
wrong ?

1. TI calculation using "charging method" where the ALA charges changes to
GLY charges (gas and solvent). I attach the xleap file for it.
  (Therefore, this method do not need to make any extra frcmod file ?)

2. Calculate the abosolute free energy changes for disappearing drug using
"disappearing method" in both the protein systems and calculate the
difference.
(This will need me to have frcmod.DH file for the drug molecule ?)

Sincerely,

Jiten
Pohang University of Sc. and Tech.
South Korea

----- Original Message -----
From: "David A. Case" <case_at_scripps.edu>
To: <amber_at_scripps.edu>
Sent: Wednesday, June 29, 2005 12:49 AM
Subject: Re: AMBER: Re: TI tutorial

> On Tue, Jun 28, 2005, Jiten wrote:
>>
>> Now looking at the first simple example (charging free energy
>> calculation),
>> the PERT.type is same with the TYPE, therfore the perturb charge will not
>> be affected. Is it a mistake or the PERT.type shoulb be kept similar with
>> what is given in the 2nd example.
>>
>> [In amber8 manual : An atom isconsidered to be perturbed if its PertType
>> is
>> different than its Type.]
>
> Did you read the full paragraph you are quoting (p. 34, top)? Immediately
> after the sentence that you quote it says:
>
> "The upshot of this is that you can change the charge of an atom without
> making the atom become "perturbed". This fits how sander works: energies
> with
> the perturbed charges are always used (if needed) independent of which
> atoms
> (if any) are marked as "perturbed".
>
> I suppose it could be clearer, but it seems to cover exactly the question
> you
> have.
>
> ...good luck...dac
>
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