Using position-dependent diffusion to simulate long colvars trajectories

From: Ajasja Ljubetič (
Date: Thu Apr 03 2014 - 07:36:28 CDT

Dear all,

When doing *free energy* calculations the *original dynamics of the colvars
is lost* as it is perturbed by the added bias. So it seems one can get
either free energy (by applying a bias) or dynamics (rate constants for
transition between states) using unbiased MD.

Wouldn't it be nice if it were possible to *obtain rate constants from free
energy calculations* as well? It turns out that this is indeed possible
under the assumptions that the colvars undergo Brownian
motion<>(i.e. the colvars
behave diffusively). The reason behind this is that the
bias does not perturb the diffusive motion of the colvars.

A few *hundred nanosecond-long biased MD* trajectory can be* extended to
millisecond* lengths in the colvars subspace at a very small additional
computational cost. First one runs the biased MD simulation to obtain the
free energy. From the biased MD trajectory of the colvars, *position
dependent diffusion coefficients *are extracted. The free energy and the
diffusion coefficients are used to simulate very long colvar trajectories.
>From the long colvar trajectories rate constants and other dynamics data
can be obtained.
(Side note: existing biased MD trajectories can be analyzed as well).

The tricky part is obtaining position-dependent diffusion coefficients.
This is the problem we tackled
 (J. Chem. Phys. 140, 084109 (2014); a PDF is available on our
We also provide an open source
calculating position dependent diffusion coefficients and generating long
diffusive trajectories.

Since many people are using NAMD with ABF or metadynamics calculations to
estimate free energies, I hope this e-mail (and the package) are useful.

Best regards,

Ajasja Ljubetič
Young researcher
Laboratory for biophysics <>
Institute Jozef Stefan, Slovenia

*Disclaimer*: In case it is not clear -- I'm the author of the mentioned
paper and package.
High level questions (eg. is this diffusive approximation even useful?:)
are probably on topic for the mailing list, but *low-level stuff* (eg.
problems with installations, etc...) should be addressed directly to me *off
the mailinglist*.

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