Reproducing free energy profile for acetate-guanidinium association

From: Grzegorz Jezierski (jezierski_at_theochem.tu-muenchen.de)
Date: Tue Nov 14 2006 - 06:40:04 CST

Dear users,

I plan to perform some free energy calculations on systems involving a
short DNA fragment complexed/bound to a chromophore molecule. I would
like to use ABF method (in NAMD), as an alternative to umbrella
sampling. Before, I tried to reproduce the results on
acetate-guanidinium association, published in J Chem Phys. (2004),
121(7); p.2904.

1.
A 2-ns ABF simulation (Xi= 4.0 --> 12.0 A) yielded strikingly different free
energy values than those in the cited paper. I tried to keep as close as
possible to the original simulation parameters. Apart from Langevin
dynamics (LD), a 2-ns 'normal' (i.e. without Langevin algorithm) MD run was
also performed. What I got was a nice looking but very shallow profile
in the case of 'normal' MD, and somewhat an anomalous profile from LD.

2.
Switching a part of harmonic restraints off didn't affect the depth of the minima; only the
asymptotic value (for large Xi) would now tend to zero.

3.
Four 0.5-ns simulations (Xi= 4.0-->6.0; 6.0-->8.0; 8.0-->10.0; 10.0-->12.0)
produced a discontinuous deltaG dependence which tends to zero for Xi=12.0A.
>From this data, estimated deltaG of dimer dissociation is about +3 kcal/mol.

4.
The important point is that I wasn't able to make the program decrease
the value of Xi. In this case, only zero deltaG values were printed to
the output file. I could only obtain non-zero result when increasing the
value of Xi (e.g. from 4.0 to 12.0 A), therefore simulating dissociation rather
than association of the complex.

Comments are welcome. Below: the ABF section of the input file.
Regards,
Grzegorz Jezierski

=======================================
abf coordinate distance-com
abf abf1 { 11 12 16 17 }
abf abf2 { 1 2 5 8 }
abf xiMin 4.0
abf xiMax 12.0
abf dxi 0.1
abf fullSamples 500
abf outfile ace_guanid_dGfinal.01.dat
abf outputFreq 100
abf historyFile abf_forces.01.dat
abf inFiles { }
abf distFile abf_distrib.01.dat
abf WriteXiFreq 100
abf ForceConst 10.0
abf dSmooth 0.4

abf RestraintList {
CNN_COO_plane1 { dihe {GUAN 2 H21} {GUAN 2 N2} {ACET 1 C2} {ACET 1 O1} 5.0 0.0 }
CNN_COO_plane2 { dihe {GUAN 2 H22} {GUAN 2 N2} {ACET 1 C2} {ACET 1 O2} 5.0 0.0 }
}

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