AMBER Archive (2005)

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

From: Jiten (jiten_at_postech.ac.kr)
Date: Sat Jun 25 2005 - 00:07:03 CDT

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

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