**From:** Diship Srivastava (*dishipsrivastava_at_gmail.com*)

**Date:** Sun Apr 25 2021 - 12:39:05 CDT

**Next message:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Previous message:**ROPÓN-PALACIOS G.: "Umbrella windows"**In reply to:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Next in thread:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Reply:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

Thanks for the answer. I have one more question - since I am doing 2D well

tempered metadynamics will the error analysis be done for both cv's

separately or is there a method to combine the error analysis for both cv

into one?

On Sat, 24 Apr 2021, 05:22 Giacomo Fiorin, <giacomo.fiorin_at_gmail.com> wrote:

*> Hi René, I think it all depends on how expensive is the system to
*

*> simulate, how complex the PMF (e.g. dimensionality, number of minima) and
*

*> most importantly, the intended use of the PMF: qualitative insight, or
*

*> actual quantification/measurement.
*

*>
*

*> If the goal is to estimate the relative probabilities of different states,
*

*> the relevant scale is dictated by the thermal energy, i.e. ~0.6 kcal/mol in
*

*> most biological applications. An estimated PMF error of 1 kcal/mol, after
*

*> exponentiating, means that the corresponding probability can very easily be *a
*

*> factor of 5 larger or smaller*. On the other hand, 0.1 kcal/mol means
*

*> that the relative error on the corresponding probability is just ~15%.
*

*>
*

*> Giacomo
*

*>
*

*>
*

*> On Fri, Apr 23, 2021 at 12:40 PM René Hafner TUK <
*

*> hamburge_at_physik.uni-kl.de> wrote:
*

*>
*

*>> Dear Giacomo,
*

*>>
*

*>> a question upon this:
*

*>>
*

*>> What would you call "long enough for today's review standards":
*

*>>
*

*>> Having convergence over serveral runs in the PMF within <1kcal/mol or
*

*>> rather on the order of (maybe a few) 0.1 kcal/mol?
*

*>>
*

*>> Kind regards
*

*>>
*

*>> René
*

*>> On 4/23/2021 5:57 PM, Giacomo Fiorin wrote:
*

*>>
*

*>> 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!rkoiprliWDa4dAvZ_C6kcdRq2hsiZJ7UaAfB8ieuMj3_8IqnfaG19QfOwKmL2BTbPw$
*

*>>> <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
*

*>>>
*

*>> --
*

*>> --
*

*>> Dipl.-Phys. René Hafner
*

*>> TU Kaiserslautern
*

*>> Germany
*

*>>
*

*>>
*

**Next message:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Previous message:**ROPÓN-PALACIOS G.: "Umbrella windows"**In reply to:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Next in thread:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Reply:**Giacomo Fiorin: "Re: Error Analysis in Metadynamics"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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