It can be very sensitive to the restraints. you need to use the exact same
reference structure for every replica, but that may not be enough. Start
with that if you didn't already.
On Thu, Sep 26, 2024, 5:35 PM Liyanage, Risi (MU-Student) <
rrlnhq.missouri.edu> wrote:
> Dear professor,
>
> Thank you very much for the valuable solution. With no cartesian
> restraints, replicas do exchange as intended. Original system had 2
> kcal/mol cartesian restraints on protein. I have tried lowering the
> restraint_wt and reducing the number of atoms in mask which has led to
> workable combination. Still, I would like to know, can there be any
> workarounds for this issue without having to use said remedies?
>
> Sent from Outlook for Android <https://aka.ms/AAb9ysg>
> ------------------------------
> *From:* Carlos Simmerling <carlos.simmerling.gmail.com>
> *Sent:* Monday, September 23, 2024 1:48:09 PM
> *To:* Liyanage, Risi (MU-Student) <rrlnhq.missouri.edu>
> *Cc:* AMBER Mailing List <amber.ambermd.org>
> *Subject:* Re: [AMBER] Calculating the number of replicas for h-remd
>
> I would try turning off restraints, especially Cartesian. See if the
> exchange improves as a way of debugging the issue. These can be tricky in
> hremd. If it fixes the problem, then you can see how to improve them.
>
> On Mon, Sep 23, 2024, 2:28 PM Liyanage, Risi (MU-Student) <
> rrlnhq.missouri.edu> wrote:
>
> Dear professor Carlos,
> Thanks for the reply.
> Yes, I am applying a harmonic restraint along the reaction coordinate in
> each replica (same anchor strength, anchor position changes). I have
> attached the colvar files to this email.
> This is a CRISPR system and has both protein and nucleic acid parts. I
> have used positional restraints on proteins and used distance restraints at
> the ends of the nucleic acid helices to prevent basepair fraying at
> terminals. I assumed it would not be an issue since they are the same for
> each replica, but maybe I am wrong.
> I have conducted nvt ensemble (no replica exchange) runs on a 4-replica
> system and looked at the reaction coordinate overlapping over time. They
> overlap very well. (I have attached the output files of this simulation)
> In order to reduce the gap between the PotE(x_1) and PotE(x_2) columns I
> have tried changing the spacing, changing the force constant but to no
> avail. I have attached the input and restraints files if needed. If I am
> correct PotE(x_1) contains the energies of the current replicas and
> PotE(x_2) contains the target energies. Current potential energies seem to
> be very close to each other, yet the target energy differ by a large amount
> form the current energy and exchange won't take place. (rem.log attached)
> How am I to get these two energies closer to each other? Thanks in advance
> for any ideas on this.
> ------------------------------
> *From:* Carlos Simmerling <carlos.simmerling.gmail.com>
> *Sent:* Saturday, September 21, 2024 6:36 AM
> *To:* Liyanage, Risi (MU-Student) <rrlnhq.missouri.edu>; AMBER Mailing
> List <amber.ambermd.org>
> *Subject:* Re: [AMBER] Calculating the number of replicas for h-remd
>
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> What is the difference in hamiltonians between neighboring replicas? You
> mention reaction coordinate, are you changing the position of a harmonic
> restraint? If yes, then the force constant is also important in addition to
> spacing.
> Look at the energy difference reported in the output you sent, it is very
> large. Does that make sense? Setting up these simulations can be tricky,
> and needs information that only you know. It also takes a good
> understanding of the principles behind HREMD, and how the exchange works.
> You might start by calculating the reaction coordinate value vs time for
> each replica, making a histogram, and seeing if they have overlap.
>
>
> On Fri, Sep 20, 2024, 4:34 PM Liyanage, Risi (MU-Student) via AMBER <
> amber.ambermd.org> wrote:
>
> Dear amber community,
>
> I am trying to run a h-remd for a relatively large system (60404 atoms
> after solvation). To create the replicas i have changed the distance
> between CoMs of two residues (as the reaction coordinate) and picked
> replicas from that. I have conducted the same simulation for a smaller
> system (setting 0.6 Angstrom reaction coordinate difference between each
> replica) and did not encounter any issues. But for the larger system I have
> tried, 0.1,0.2,0.3,0.4 angstrom differences but still not getting any
> replica exchanges. Infact left_fe, right_fe keep showing '-infinity'
> (picture attached). Since h-remd is said to be less dependent on the number
> of replicas (as opposed to t-remd) with the increasing system size, this
> problem is quite difficult for me to understand. Can anyone give me an idea
> about this issue or propose a way to calculate the number of replicas for
> h-remd?
>
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Received on Thu Sep 26 2024 - 15:00:02 PDT
