RE: Runaway positive feedback when minimizing large systems (was: strange glitches when performing energy minimization in MDFF simulations)

From: Tristan Croll (tristan.croll_at_qut.edu.au)
Date: Wed Feb 19 2014 - 17:53:43 CST

Hi all,

Just wondering if anyone's had a chance to look at this?

My own observations from watching a few different-sized simulations minimize in IMD Connect after doing various perturbations to different residues:

- For some reason that's not entirely clear (perhaps floating-point errors as the total system energy gets very large?), minimization in general gets more "jumpy" (i.e. atoms move further with each minimization step) as the system size increases;

- In some (fairly rare) cases, this leads to a temporary runaway in the algorithm as a small initial deviation is magnified into a very large local disturbance, which can lead to cis/trans or chirality flips before settling;

- The "runaway" effect seems to only occur in a few different situations - so far I've only been able to replicate it reliably in solvent-exposed asparagine residues (by changing the length of the side-chain C=O bond) and in histidines (by moving the side-chain nitrogens slightly closer together). Similar scale changes in other residues still lead to transient deviations larger than what one would expect to see in a smaller-scale simulation, but these are usually brought under control quite quickly (I've by no means done an exhaustive check of different residues, though). In both the asparagine and histidine cases, I've seen such runaways arise in re-minimization of structures that had undergone extensive minimization, indicating that structural deviations within (but at the outskirts of) normal ranges can trigger the problem.

- I've replicated the same behaviour in NAMD versions 2.8 and 2.9, on a cluster (ibverbs) build and on my local workstation, in both CUDA and non-CUDA builds, and in both CHARMM 27 and 36 forcefields.

- Perhaps most strangely, I had more trouble replicating the runaway behaviour in the STMV benchmark than in the ATPase benchmark.

Anyway, a fairly straightforward workaround for anyone who's worried is to always do a few thousand steps of backbone-restrained minimization first, even if you're just re-minimizing a previously equilibrated system.

Cheers,

Tristan

-----Original Message-----
From: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] On Behalf Of Tristan Croll
Sent: Thursday, 13 February 2014 9:51 AM
To: Bennion, Brian; Norman Geist; namd-l_at_ks.uiuc.edu
Subject: namd-l: RE: Runaway positive feedback when minimizing large systems (was: strange glitches when performing energy minimization in MDFF simulations)

Hi Brian,

I'll go one better. At the link below I've put together a demonstration simulation. It's based on the ATPase benchmark, and the only thing I've done is moved the OD1 atom on ASN33 of segname PSLN by roughly 0.2A.

- Untar into a directory of your choice
- load f1wations_xplor.psf / f1wations-pme-nve-200ps_PSLN_33_OD1_moved.pdb in VMD
- visualise "segname PSLN and resid 33" and "same residue as within 10 of (segname PSLN and resid 33)" in your choice of representation, and center your view on the former
- run namd using the config file f1atpase.namd
- In VMD, go to Extensions/Simulation/IMD Connect
- enter "localhost" in the Hostname box and 2030 in the Port box
- after allowing some time for the simulation to set itself up, click Connect
- enjoy (?) the show.

Cheers,

Tristan

https://www.dropbox.com/s/zqa9qwy60v2bd4x/f1atpase_min_glitch.tar.gz

-----Original Message-----
From: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu] On Behalf Of Bennion, Brian
Sent: Thursday, 13 February 2014 2:57 AM
To: namd-l_at_ks.uiuc.edu
Subject: namd-l: RE: Runaway positive feedback when minimizing large systems (was: strange glitches when performing energy minimization in MDFF simulations)

Hello Tristan,

In one of you posts you showed a histidine oscillating. can this be replicated with any histidine in your autoimd tests?

Does the asp need to be in the center of the box to be show the behaviour?
Would you mind posting your autoimd config files and I will have a go at it

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