# AMBER: PMF calculation with gibbs

From: Xiao Jian Tan <xjtan.u.washington.edu>
Date: Wed, 27 Aug 2003 15:34:16 -0700 (PDT)

Dear amber users,

Currently I am doing PMF calculations with Gibbs of AMBER-6. I got some weird results, and can not figure out what was going on there. Also there are very few documents available. I was wondering if anyone can help me.

My system has about 30,000 atoms, including protein, ligand and TIP3P water box. I'd like to see how large the free energy penalty is when I change two internal torsion angles of the ligand (These changes are not dramatically, for each torsion, ~25 degree, but the energetic effect is significant!). I first did the PMF calculation using torsional constraints (ITOR=2), TI method, cutoff = 10 A, 21 windows and 525 ps for the whole calculation. But the outcome free energy is –1.8 kcal/mol, which is in contras with the experimental observation. Since the umbrella sampling may do a better job, then I tried another PMF calculation using FEP method, IUMB=1, ITOR=0, cutoff=10, 21 windows and 525 ps sampling in total. But this time the free energies I got are all zero for each window.

In order to find out the reason, I did some test PMF calculations using ethane, a very simple system, to explore the free energy difference between the stagger and eclipse conformational states. Similarly, I first using ITOR=2, TI method, cutoff = 10 A, 21 windows and 2050 ps for the vacuum system. The calculated free energy change from stagger state to eclipse state is about 2.9 kcal/mol. It looks reasonable to me. But when I tried Umbrella sampling, it always gave zero no matter what I specified for ITOR( 0 or 1), IZE (0 or 1).

So my questions are:

1. what is the best way to perform a PMF calculation?
2. why does the umbrella sampling have such behaviors?
3. Could you provide me some suggestion about my system? Why I did not get the right answer?

Thanks, Xiaojian

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Received on Wed Aug 27 2003 - 23:53:01 PDT
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