**From:** Giacomo Fiorin (*giacomo.fiorin_at_gmail.com*)

**Date:** Fri Apr 23 2021 - 10:57:34 CDT

**Next message:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Previous message:**Raman Preet Singh: "Advice on hardware for NAMD"**In reply to:**Miro Astore: "Re: Error Analysis in Metadynamics"**Next in thread:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Reply:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

Hi Diship, it highly depends on what error analysis you plan on doing. The

approach that I and others use with metadynamics has very few assumptions:

after estimating that the systems has explored all relevant states at least

once, start collecting the PMF at regular intervals and simulate for

additional time such that all states are visited a few more times, i.e. a

few more layers of Gaussian hills are added on top of the converged PMF.

Then just compute the average and SD of the free-energy over the sample of

multiple PMFs, which are only text files, so you can do the following:

all_pmfs = np.zeros(shape=(n_files, n_points))

for i_file in range(n_files):

_, pmf = np.loadtxt(pmf_file_names[i_file], unpack=True)

all_pmfs[i_file,:] = pmf[:]

pmf_mean = all_pmfs.mean(axis=0)

pmf_SD = all_pmfs.std(axis=0)

The tutorial that Miro has linked uses block averages, where the additional

difference is that the length of the blocks is also varied to converge the

SD. You should see for yourself that the dependence of the SD on the block

length is rather slow (in theory, it should follow a square root).

Having said all that, here you're not simulating something trivial like

dialanine isomerization: any meaningful error estimate will require that

the CV has already visited all states repeatedly during the simulation. If

you can see such trajectory, then you're in good shape and any PMF method

including metadynamics will give you unbiased results. If you ran long

enough for today's review standards, your statistical error bars will be

comparable or smaller than the size of the marker used in the plot :-) You

ought to be able to explain how you computed the statistical error bars,

but these ought to be very small or downright negligible.

On the other hand, if the CV is not a good reaction coordinate any error

analysis will be uninformative: you need to analyze the atomic trajectory

and show that at any given frame the structural properties (e.g.

coordination with water or lipids) depend only on the value of the CV, but

not on the simulation history. Any inconsistency that you may see there

may not easily be solved with longer simulation times.

In short, statistical sampling is less of an issue than it used to be (the

most common PMF methods are now at least two decades old!), but *picking a

good CV* has always been "the big deal", where your insight into the

specific problem matters the most.

Giacomo

On Tue, Apr 20, 2021 at 3:37 AM Miro Astore <miro.astore_at_gmail.com> wrote:

*> Hi Diship, you should be able to use the code/techniques in this tutorial.
*

*> Good luck.
*

*>
*

*> https://urldefense.com/v3/__https://www.plumed.org/doc-v2.5/user-doc/html/trieste-4.html__;!!DZ3fjg!oP-_Zk-rfJChIEjBoYdFZ4a-Y4DgRZdCY9AUJTqbm92S-vv-5rzsvY3QhKNr8w0SoQ$
*

*> <https://urldefense.com/v3/__https://www.plumed.org/doc-v2.5/user-doc/html/trieste-4.html__;!!DZ3fjg!sp8OPR83ZO7SNR9X9YYdw-9CIV1DXCkkqKUva3mWJ5o6ou3SWvonbwVzjmecWx3n9w$>
*

*>
*

*> On Tue, Apr 20, 2021 at 4:41 PM Diship Srivastava <
*

*> dishipsrivastava_at_gmail.com> wrote:
*

*>
*

*>> Hi,
*

*>> I have done well tempered metadynamics for a system consisting of a
*

*>> molecule insertion into a bilayer using the colvars module. I am
*

*>> interested in doing an error analysis for obtained free energy
*

*>> preferably using colvars.
*

*>> Any help would be most appreciated.
*

*>>
*

*>> Thanks in advance
*

*>>
*

*>>
*

*>>
*

*>> --
*

*>> Diship Srivastava
*

*>> JRF
*

*>> Department of Chemistry
*

*>> IIT(ISM) - Dhanbad
*

*>> India
*

*>>
*

*>
*

*>
*

*> --
*

*> Miro A. Astore (he/him)
*

*> PhD Candidate | Computational Biophysics
*

*> Office 434 A28 School of Physics
*

*> University of Sydney
*

*>
*

**Next message:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Previous message:**Raman Preet Singh: "Advice on hardware for NAMD"**In reply to:**Miro Astore: "Re: Error Analysis in Metadynamics"**Next in thread:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Reply:**René Hafner TUK: "Re: Error Analysis in Metadynamics"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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