Re: Proposed Feature in Targeted MD

From: V.Ovchinnikov (
Date: Mon Jan 31 2011 - 15:14:15 CST

Dear David,

I have tinkered with the restrained version of TMD that is in NAMD2.6 a
couple of years ago, and I think I have a version that performs a
double-sided TMD using two orientation structures, as you describe
(although I was not using it to compute work, just to look possible
paths). If you give me a couple of days to dig up the relevant files, I
can send them to you off-the-list. Not quite sure how the TMD 2.7 source
code is different from TMD 2.6, but I would be surprised if the
differences were large. (One could polish the code and submit to the
developers for inclusion later, too, if the community thinks its


On Mon, 2011-01-31 at 13:12 -0600, Minh, David D. wrote:
> A minor change to targeted MD can make it possible to calculate
> potentials of mean force in the region between two structures.
> Right now, the code allows targeting toward one final structure, with
> the potential given by the following equation,
> U_{TMD} = \frac{1}{2} \frac{k}{N} [ RMS(t) - RMS^*(t) ]^2
> It should be relatively easy to modify targeted MD and have the option
> of targeting the transition between two structures. The potential
> would be,
> U_{TMD} = \frac{1}{2} \frac{k}{N} [ DRMS(t) - DRMS^*(t) ]^2,
> with DRMS(t) = RMS_1(t) - RMS_2(t), and RMS_1 being the RMSD from
> structure 1 and RMS_2 being the RMSD from structure 2, and DRMS^*(t)
> being a time-dependent function. This bias was used in,
> NK Banavali and B Roux. Free Energy Landscape of A-DNA to B-DNA
> Conversion in Aqueous Solution. J. Am. Chem. Soc. 127(18), 6966-6876
> (2005).
> K Arora and CL Brooks. Large-scale allosteric conformational
> transitions of adenylate kinase appear to involve a population-shift
> mechanism. PNAS 104(47), 18496-18501 (2007).
> and probably other papers.
> Using the theory described in,
> G Hummer and A Szabo. Free energy reconstruction from nonequilibrium
> single-molecule pulling experiments. PNAS 98(7), 3658-61 (2001).
> one could calculate the PMF along the DRMS coordinate from a set of
> TMD trajectories. The theory described in,
> DDL Minh. Multidimensional Potentials of Mean Force from Biased
> Experiments along a Single Coordinate. J. Phys. Chem. B 111,
> 4137-4140 (2007).
> can be used to calculate the PMF along other coordinates, or 2D PMFs.
> The theory in,
> DDL Minh and AB Adib. Optimized Free Energies from Bidirectional
> Single-Molecule Force Spectroscopy. Phys. Rev. Lett 100(18), 180602
> (2008).
> DDL Minh and JD Chodera. Optimal estimators and asymptotic variances
> for nonequilibrium path-ensemble averages. J. Chem. Phys. 131(13),
> 134110 (2009).
> would be useful for combining data for the transition from structure 1
> to structure 2 and the reverse process from structure 2 to structure
> 1.
> Actually, it is possible to reconstruct PMFs with the current TMD
> code, but I think the PMF between two structures would be more
> interesting.
> I'd like to give this a try. Would any NAMD developers be interested
> in making this modification? Any thoughts?

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