AMBER Archive (2008)

Subject: AMBER: TI calculations in Amber10

From: Samuel Genheden (a03samge) (a03samge_at_student.his.se)
Date: Wed Jun 25 2008 - 06:58:28 CDT

Hello, Amber users
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I'm trying to calculate relative binding free energies of two drug molecules using the TI facilities in Amber10. The perturbation is an O-atom to a NH-group. I've followed the tutorial "small molecule binding to T4-lysozyme" and therefore breaked up the perturbation in 3 steps: 1) remove charge of O-atom, 2) transformation of neutral O-atom to neutral NH-group with soft-core potential and 3) addition of charge to NH-group. I have used 9 lambda values from 0.1 to 0.9. The experimental difference in binding energy is very small, in the order of 1 kcal/mole. The 1:st and the 3:rd steps seemed to work okey since the deltaG are on the order of 0.1 kcal/mole. However the problem is in the 2:nd step where I get unreasonable high dv/dl values, both in the protein and in the water phase. Here the dv/dl are about 15-30 kcal/mole and deltaG evaluates to approx. -20kcal/mol. Here is an example of the input file for the production run:

Production
 &cntrl
  irest=1,ntx=5,
  nstlim=1000000,dt=0.002,
  temp0=300.0,ntt=3,gamma_ln=2.0,
  ntc=2,ntf=1,
  cut=8.0,
  ntpr=5000,ntwx=5000,ntwv=0,ntwe=5000,iwrap=1,
  ntb=1,
  ipol=0,igb=0,
  scnb=2.0,scee=1.2,
  ntr=0,
  icfe=1, clambda = 0.5,
  ifsc=1,
  crgmask=':CBB_at_032',
  scmask=':CBB_at_O32',
 &end

I hope someone can shed some light on my problem, and maybe point to possible sources of error.

Best regards,
Samuel

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