VMD-L Mailing List

From: Rune Thomas Kidmose (rtk_at_mbg.au.dk)
Date: Wed Feb 28 2018 - 13:43:33 CST

Hi Josh,

Sorry for the late answer.

Yes I have used COLORES for that many times and I really like it especially because it is so easy to run from cmd-line, however I have never heard of the other two programs.

I was looking for a way of performing MDFF on an unaltered protein that have only been rigid fitted into a density, so no individual fitting of the domains etc. I have done this a couple of times now, but every time I try it on a target that needs large rotations it seems to fail.

As mentioned earlier, I get that large domain rotations are not easy for MDFF to "solve", so I was basically just checking that I had not missed some setting or feature in MDFF that would make dealing with large rotations easier.

As Ryan suggested I have also tried low-pass filtering the target densites (to like 15 or 20Å), and that actually helps some times, but large domain rotations are not resolved by this, at least not in my hands.

However, it is not only large rotation I sometime have problems with, as an example I tried to MDFF the closed conformation of CorA channel (3jcf) into the low res density of one of the open conformations of the channel (3jch).

I have made a video of the fitting and dropped it on youtube for those who might be interested.

https://youtu.be/eXbK-KkEZr4

Here you can see, I hope, how some of the long helices does not move into the "correct" density, which results in the whole domain, that needed to flip into the density, is stuck at a intermediate position.

I have tried many different variations of MDFF parameters for this run, mainly playing with the G-scale (from 0.05 to 5) , numsteps (70.000 to 500.000), initial vs final temp, and I have never been able to get it right, though I get pretty close sometimes.

Again I have not used domain restraints or individually fitted any of the domains, as they did in the original paper of the structures. I "just" wanted to do MDFF on a deposited model of the closed conformation rigid fitted into the open conformation, but I have not been able to do that. Maybe this is a good case for low-pass filtering the target density, despite it relativ low res to start with (7'ish Å).

Cheers

Rune

 

________________________________________
Fra: Vermaas, Joshua <Joshua.Vermaas_at_nrel.gov>
Sendt: 26. februar 2018 17:32
Til: Rune Thomas Kidmose; Ryan McGreevy
Cc: vmd-l_at_ks.uiuc.edu
Emne: Re: Sv: vmd-l: MDFF rotation

Hi Rune,

Have you tried getting the domains prefit independently into the density, either with COLORES from Situs or newer EM-fitting programs like GEMfitter or BCL::EM-Fit? Then MDFF can fix up some of the small structural changes, letting the other programs get you in the right ballpark. It sounds like you are trying to take a structure that is misaligned to the initial density, which is going to be needlessly slow to converge rather than starting from a density-structure pair that are properly aligned.

-Josh

On 02/26/2018 08:15 AM, Rune Thomas Kidmose wrote:

Hi Ryan,

thx for getting back.

Yes I have played a lot with the domain restraints feature as well, and for a few cases, as the one shown in the tutorial, it kinda works, but not for all.

In general, I find the way you have to specify the domains using beta and occupancy values, to be a very slow'ish procedure for larger PDB files with many domains. But that is a different story I guess.

Ruki

________________________________
Fra: Ryan McGreevy <ryanmcgreevy_at_ks.uiuc.edu><mailto:ryanmcgreevy_at_ks.uiuc.edu>
Sendt: 26. februar 2018 14:47
Til: Rune Thomas Kidmose
Cc: vmd-l_at_ks.uiuc.edu<mailto:vmd-l_at_ks.uiuc.edu>
Emne: Re: vmd-l: MDFF rotation

Have you tried using domain restraints (an example is in the MDFF tutorial)? This should help the domain fit together rather than the usual piecemeal approach.

On Mon, Feb 26, 2018, 4:48 AM Rune Thomas Kidmose <rtk_at_mbg.au.dk<mailto:rtk_at_mbg.au.dk>> wrote:

Hi all,

I have been tinkering with MDFF for the past half year now, and I have accumulated a couple of questions, one of which is:

Is it possible to somehow make MDFF handle large rotations of the initial model when fitting to the target density? It seems MDFF progresses quite linearly in its fitting, so is there a way to tell it or help it rotate e.g. a domain?

I have come across a couple of cases where a domain clearly should be rotated significantly to fit the density, but MDFF just kept on pushing it into the density and then proceeded to fill the density by pulling in the domain. I am not thinking about iMDFF, where you manually interact with the model, which currently is the only way that worked for me.

I acknowledge that rotation during MDFF it is not a trivial problem to solve but maybe I have missed some thing?

Cheers

Ruki