[AMBER] PMF problem

From: dhacademic <dhacademic.gmail.com>
Date: Tue, 1 Feb 2011 15:55:30 -0500

Hi everyone,

I have a problem in 2D PMF calculations.

There are two reaction coordinates (RC) in my system. RC1 stands for
conformational change of protein (RC1 ranges from 1 to 10, where RC1=1 means
closed state of protein, RC1=10 means open state), and RC2 is the distance
between ligand and active site (RC2 ranges from 1 to 10, where RC2=1 means
ligand bound state, RC2=10 means ligand escaped state). After the
time-consuming umbrella sampling calculations (with amber9) on two RCs, the
2D free energy profile can be obtained with WHAM program. However, the open
state of protein with ligand bound to active site (RC1=10, RC2=1) is found
to be a minimum on the free energy surface, while the closed state with
ligand bound has higher energy (RC1=1, RC2=1). This is opposite to what I
have expected, where the closed state of protein with ligand bound should be
a stable state.

Then the umbrella sampling data of different RC1 (from 1 to 10) with fixed
RC2 (RC2=1) are used to get quasi-1D free energy profile of protein
conformational change with ligand bound, and the results seem to be
reasonable: the open state is energetic unfavorable, and the closed state
has a minimum. The system stability in quasi-1D free energy profile is

Besides, umbrella sampling on RC1 (no bias potential is imposed on RC2, and
the ligand position and orientation is almost unchanged because there are
lots of favorable interactions between ligand and active site is strong) was
done on the same system. The generated 1D-PMF results is quite similar to
the quasi-1D one, and quite different to the 2D-PMF results when RC2=1.

All the structures as well as the data have been carefully checked.
Everything looks good, but the results look strange. I do not understand why
the stability of the system in 2D-PMF and quasi-1D-PMF is different. As the
results from 2D-PMF are inconsistent with common knowledge of protein-ligand
complex, I think there may be something wrong with my 2D-PMF calculations.
Can anyone give some suggestions? Thanks in advance!


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Received on Tue Feb 01 2011 - 14:30:02 PST
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