[gmx-users] The Rationality of Position Restrain in Umbrella Sampling

[Jason Zhu]

Dear All,

I am modeling the free binding energy between two molecules following the
Gromacs Tutorial 3: Umbrella Sampling (
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin/gmx-tutorials/umbrella/index.html
).

In this tutorial, the Chain_B of proteins is fixed as an immobile reference
by position restrain during not only the stage of Steered MD but also the
stage of Umbrella Sampling.

I am wondering what the rationality of the position restrain is for the
calculation of free energy. Does this reduce of degree of freedom due to
the position restrain have any artificial influence on the calculated free
energy?

Why don't we just use "COM motion removal" method to fix the COM of the
protein complex and use pulling method to separate the Chain_A from other
protein chains? Is it because of the excessively strong binding between
them? If we use position restrain, do we need to make some corrections to
the calculated binding free energy, just like the below paper?

Boresch, S., Tettinger, F., Leitgeb, M., and Karplus, M. (2003) Absolute
binding free energies: A quantitative approach for their calculation. J.
Phys. Chem. A 107, 9535–9551
(http://pubs.acs.org/doi/abs/10.1021/jp0217839)

Best,
Wenpeng Zhu