[AMBER] How to simulate hydration free energy with thermodynamic integration?

From: Junjian Miao <junjianmiao.gmail.com>
Date: Fri, 18 Feb 2011 21:45:49 +0800

Hi all,


Recently I have simulated benzene to estimate its hydration free energy, for the removing charge step, I can create the simulation files and modeling correctly. however, for the second step of the removal vdW, I don¡¯t know how to generate the simulation files. the following is my attempt of removal vdW step.


for simulating hydration free energy, on the basis of literatures, one can design thermodynamic cycle as follows:



in terms of above processes, the following equation can be obtained



Now I will display an example of benzene for LJ step.


(1) tleap -f leap.in













(2) cp benw.prm benwv.prm

   cp benw.rst benwv.rst

then modify LENNARD_JONES_ACOEF and LENNARD_JONES_BCOEF within benwv.prm file to 0.00.

I use these four files to simulate(not use softcore, i.e. ifsc=0), for lambda=0.1,0.2,0.3,0.4, the simulations work. I inspect the DV/DL variable, the values are very large, up to -2000.

for larger lambda, the simulations fail, the error information reads as follows



            Cutoff list exceeds largest sphere in unit cell!!

             Big problems with imaging!!

             a,b,c = 24.5236717948086 25.2079298792356


             alpha,beta,gamma = 90.0000000000000 90.0000000000000


             cutlist,sphere = 11.0000000000000 10.9999500560932










when i modified ¡°solvatebox BNZ SPCBOX 10¡± to ¡°solvatebox BNZ SPCBOX 12¡±, the identical error print too.


So, there are two questions

(1) How to create simulation files for the LJ step? in the simulation, whether use softcore or not?


(2) For the non-hydrated benzene, do we also use periodic boundary conditions?


please give your suggestion and your detail operations. thank you very much!


Best regards,


  Junjian Miao

  School of Chemisty and Chemical Engineering

  Nanjing University

  Jiangsu province, China

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Received on Fri Feb 18 2011 - 07:00:04 PST
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