Hi Aravind,
NEB is a path sampling method that's used to examine the transition between
two well-defined endpoints. It does not impose a barrier - the system's
transition over this barrier is the limiting factor in sampling the
open-to-close transition, and this is what/why you are trying to
calculate the path (and potential energy) independent of timescale.
It seems like you're doing some stuff to try and get this working for your
system, like increasing/changing the number of starting images, generating
intermediates using TMD, etc.
There is no "standard" way to run these simulations, unfortunately. Each
system is different, each underlying potential energy surface is different.
I do have a few additional suggestions, which may help:
-Try explicit solvent.
-Extend the initial 1HEAT step to be more gradual (Try 1ns? 40ps is short,
and might be ok for alanine dipeptide but not for everything).
-Add an equilibration step after the first heating step (500 ps, 1 ns?)
-Add images at the intermediate to try and avoid discontinuities in the
transition, this could help avoid those initial 'NaN' values.
Look at Test Case 3 in this paper and change up the original inputs to
match what they do (a similarly large system's protocol could be more
relevant to your own problem):
https://pubs.acs.org/doi/10.1021/acs.jctc.9b00329
The real struggle is getting a nice interpolating initial path. I'd
recommend spending time on that first, then troubleshooting any other
problems that arise.
Good luck!
-Christina
On Fri, Oct 21, 2022 at 2:18 AM Aravind R via AMBER <amber.ambermd.org>
wrote:
> Hi Amber Developers/ Users,
> I am performing NEB, moving the system from its "Open" structure to the
> "Close" structure. This comprises of large conformational transition.
> I had minimised the initial and final structures until convergence before
> starting NEB.
>
> I have played around with spring constants ( skmin/skmax ranging from 0.5
> to 50 at various stages), temperatures (slow to fast heating & slow
> cooling) and the number of images to represent this transition (I performed
> TMD to sample images from open to close transition. Used conformations from
> TMD to represent the number of images I supply NEB to start with - I used 8
> - 64 images to represent transition with just 2 to 32 conformations from
> TMD).
>
> I performed implicit solvent NEB in 6 stages:
> 1HEAT - spring constant
> ranging from 0.5 - 10 for 40ps of MD with a 0.5fs time step raising temp
> from 0 to 300K
> 2ANNEAL - spring constant
> ranging from 1 - 50 for 1ns of MD with a 1fs time step raising temp from
> 300 to 500K
> 3EQUIL - spring constant
> ranging from 1 - 50 for 2ns of MD with a 2fs time step equilibrating at
> 500K
> 4COOL - spring constant
> ranging from 1 - 50 for 2ns of MD with a 2fs time step decreasing temp from
> 500 to 300K
> 5EQUIL - spring constant
> ranging from 1 - 50 for 2ns of MD with a 2fs time step equilibrating at
> 300K
> 6COOL - spring constant
> ranging from 1 - 50 for 2ns of MD with a 2fs time step decreasing temp from
> 300 to 0K
> 6EQUIL - spring constant
> ranging from 1 - 50 for 2ns of MD with a 2fs time step equilibrating at 0K
> **spring constant ranging from x - y: is across different attempts not in a
> single simulation.
> I am having the following issues:
> 1) Irrespective of the values I play around with, NEB constantly
> imposes a barrier height. This leads to the unfolding of the helix in the
> region I try to perform the tgtrmsmask in.
>
> 2) At the images Where the conformational transition is sampled, the
> energies go very high and the potential energy gets to NaN (This mostly
> happens due to the helix unfolding raising dihedral and vdw energies to
> shoot up).
>
> 3) Even though I used 32 evenly spaced conformers (sampling the
> transition) from TMD to sample 64 images in NEB, the transition is not
> smooth, with a sudden drop in energy for the last but one conformer. This
> drop in energy moves towards the left as I decrease the number of
> conformers I use to represent transition. For eg: If I just use open and
> closed conformers (as in the tutorial), the dip in the energy is in the
> centre image. As I increase the Conformers from TMD the dip move towards
> the right from the centre. To negate this I tried an unequal number of
> images used to represent transition: the first 4 images were sampled from
> "Open" and the rest from "Close", and so on and so forth.
>
> Any help is appreciated !!!
>
> Regards,
> Aravind R
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
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Christina Bergonzo
Research Chemist
Biomolecular Measurement Division, MML, NIST
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Received on Fri Oct 21 2022 - 06:30:02 PDT
