AMBER Archive (2005)

Subject: Re: AMBER: TI-FEP for ALA --> GLY

From: Ilyas Yildirim (yildirim_at_pas.rochester.edu)
Date: Sat Jun 25 2005 - 01:48:36 CDT

Hi Jiten,

The frcmod file u created looks ok, but why do u have 0 mass on the dummy
atoms? I would have chosen the hydrogen mass rather than a zero mass for
the DH atom.

Second thing, did u check out one of the trajectory file to see if
everything is ok? And also, what are your dv/dl results for these 12
lambda values. I have done a simple free energy calculation for
ethane->methane which looks similar to what you have done (-CH3 changes to
H-DH3). I also got a result which was close to zero. I did the simulation
just for a test purpose. I have used explicit solvent. In order to compare
with something real (with an experimental data), u have to do 2 different
TI simulation: One in a solvent, the other in gas phase, and take the
difference of these results. That will give u a prediction for an
observable. (Thermodynamic Cycle)

For the ethane->methane case, the solvation of ethane and methane are
almost the same, so it is reasonable to expect something close to zero.
What is the solvation free energies of ALA and GLY (or the solvation free
energies of the initial and final states of your system)? The difference
of these energies should be equal to the free energy change of the
transformation in a solvent subtracted from the free energy change of the
transformation in gas phase.

Good luck,

On Sat, 25 Jun 2005, Jiten wrote:

> Dear Amber users
>
> For my protein-drug system : while doing the free energy peturbation using TI method using 12 windows, and using the perl script attached here, I got almost zero difference in free energy. I used the following atom types, where DH is dummy atom with zero charge and the charges of the alaline is replaced by glycine charges in the pert.charge options
>
>
> H1 HC H0 DH
> | | | |
> --CT---CT--HC ---> --CT --H0--DH
> | |
> HC DH
>
> My frcmod.DH is as follows,
>
> ALA to GLY
> MASS
> DH 0.000
>
> BOND
> H0-DH 340.0 1.090 !CT-HC
>
> ANGLE
> DH - H0 - DH 35.0 109.50 !HC-CT-HC
> CT - H0 - DH 35.0 109.50 !HC-CT-HC
>
> DIHE
> - The default values as given by leap
> --
> --
>
> NONB
> DH 0.000 0.00
>
> Am I doing something stupid here ? Do I need to set the Bond and angles : K and R values as zero ?
>
> However, I calculate the absolute free energy of the two syatems using MM-PBSA from the last 1ns trajectory of the 2ns MD simulations (well converged - rmsd, temp and energy) and I got that there is clear differences between the two protein systems.
>
> ELE -8.99 -8.96
> VDW -41.125 -37.68
> GAS -50.115 -46.64
> PBSUR -3.025 -3.07
> PBCAL 27.105 24.16
> PBSOL 24.09 21.09
> PBELE 18.12 15.2
> PBTOT -26.025 -25.55
> TSTOT 12.675 15.79
> PBTOT-S -13.35 -9.76
>
>
> Thanks for any suggestions,
>
> Sincerely,
>
> N. Jiten Singh
> C/O Prof. Kwang S. Kim
> Department of Chemistry
> Pohang University of Science and Technology
> San 31, Hyojadong, Namgu
> Pohang 790-784, Korea
> Phone : 82-54-279-5853 ( Lab ) / 279-4138 ( Appt )
> Fax : 82-54-279-8137 (or +82-54-279-3399)
> Web : http://csm.postech.ac.kr/ and http://www.postech.ac.kr/e
> Home Page : http://www.geocities.com/njs_19 

-- 
  Ilyas Yildirim
  ---------------------------------------------------------------
  - Department of Chemisty       -				-
  - University of Rochester      -				-
  - Hutchison Hall, # B10        -				-
  - Rochester, NY 14627-0216     - Ph.:(585) 275 67 66 (Office)	-
  - http://www.pas.rochester.edu/~yildirim/			-
  ---------------------------------------------------------------

-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu