RE: hbond restraint simulation

From: Vermaas, Joshua (Joshua.Vermaas_at_nrel.gov)
Date: Mon Jan 28 2019 - 15:23:57 CST

Hi Prabir,

Do you think it would help to switch things over to hbonds? My only advice is to be creative. You've identified a problem, and now you want to reform hydrogen bonds+keep some new ones. Read though how to enforce that in colvars, and I think you are well on your way.

-Josh

On 2019-01-27 15:34:16-07:00 Prabir Khatua wrote:

Hi Josh,

Thank you very much for your suggestion. Using distance restraint indeed speeded up the process. I used a combination of hbond and distance restraints
to do the simulation. Individual monomers were pulled up within a reasonable time by targeted MD with a force constant of 20 kcal/mol A-2. However,
it seems that some of the hbonds which were already present before pulling got affected due to inappropriate orientation after this process though no reasonable deformation of the molecules took place. Please note that I used hbond restraints for the bonds which were already hbonded. Can you please suggest me what to
do at this situation to obtain the required structure? The required structure mainly relies on hbonds, as it is a barrel-shaped structure that is basically formed by anti-parallel beta-sheets. Do you think whether it would help on restarting the simulation at this point by changing the distance restraints to hbonds as the donor-acceptor distance is now within 3.3 A?

Sincerely,

Prabir

On Mon, Jan 28, 2019 at 4:01 AM Prabir Khatua <prabir07chem_at_gmail.com<mailto:prabir07chem_at_gmail.com>> wrote:
Hi Josh,

Thank you very much for your suggestion. Using distance restraint indeed speeded up the process. I used a combination of hbond and distance restraints
to do the simulation. Individual monomers were pulled up within a reasonable time by targeted MD with a force constant of 20 kcal/mol A-2. However,
it seems that some of the hbonds which were already present before pulling got affected due to inappropriate orientation after this process though no reasonable deformation of the molecules took place. Please note that I used hbond restraints for the bonds which were already hbonded. Can you please suggest me what to
do at this situation to obtain the required structure? The required structure mainly relies on hbonds, as it is a barrel-shaped structure that is basically formed by anti-parallel beta-sheets. Do you think whether it would help on restarting the simulation at this point by changing the distance restraints to hbonds as the donor-acceptor distance is now within 3.3 A?

Sincerely,

Prabir

On Sat, Jan 26, 2019 at 3:31 AM Vermaas, Joshua <Joshua.Vermaas_at_nrel.gov<mailto:Joshua.Vermaas_at_nrel.gov>> wrote:
Hi Prabir,

Keep your questions on the list, so that others can benefit/correct me if I give bad advice (Thanks Lennart!). :)

Since the range on Hbond is so small, you tend to need a huge force constant to go with it. I think I've used values in the thousands before. Its needed because it depends on the contact number formula, which can have small gradients despite being far from where you want to be, reducing their effectiveness. If you really want to stick with hbonds, you'll need to increase your force constant, and set the current value and target to be 1.0. Distance collective variables are nice and simple, with consistent gradients that push towards your target no matter how far away you are, and can be used in conjunction with hbonds restraints (colvars is super flexible that way). I've sometimes used upperWall half-harmonic potentials too, since you only really care that the distances get close, not really how close they are. You may also want to consider a RMSD-based restraint so your individual monomers don't deform as they are being moved.

-Josh

On 2019-01-25 13:34:34-07:00 Prabir Khatua wrote:

Hi Josh,
Thank you very much for your answer. Actually I already have a template tetramer structure that was obtained by simulation. That is why I wanted to use the same for constructing hexamer
by doing a restraint simulation. I have a small query about the colvar switch from hbond to distance. Will hbond restraint work fine if I somehow manage to bring the respective hbond forming
atoms within 3.3 A? One more thing, please let me know if I can use hbond and distance restraint together.
Thanks,
Prabir

On Fri, Jan 25, 2019 at 2:09 PM Vermaas, Joshua <Joshua.Vermaas_at_nrel.gov<mailto:Joshua.Vermaas_at_nrel.gov>> wrote:
Hi Prabir,

While I'm normally a big advocate for letting the force field figure things out, I'd try to get something reasonable first by any means necessary. If you know that the hexamer has some symmetry, I'd exploit that symmetry. Assuming a monomer that is correctly oriented and everything is 60 degrees apart on the wheel something like the following will get you close to a barrel structure:

set monomer [atomselect top "whatever you need to get a monomer selected"]
$monomer moveby [vecscale -1 [measure center $monomer]]
$monomer moveby [list 20 0 0]; #Adjust as needed. The "20" is basically your barrel radius
$monomer writepdb A.pdb
$monomer move [transaxis z 60]
$monomer writepdb B.pdb
#Continue doing this until you have your 6 monomers arranged how you want.

However, that doesn't actually answer your original question. The problem is that a "hbond" colvar only goes between 0 and 1 (see http://www.ks.uiuc.edu/Research/namd/2.13/ug/node55.html#SECTION0001241160000000000000), since a hbond either exists or it doesn't (with a switching function inbetween). Your targets are all too large, so the colvar isn't doing what you want. Change all your "hbond" definitions to "distance", and I think you are in business.

-Josh

On 2019-01-25 12:24:26-07:00 owner-namd-l_at_ks.uiuc.edu<mailto:owner-namd-l_at_ks.uiuc.edu> wrote:

Dear NAMD user,
I am trying to prepare a barrel-shaped oligomer of a protein starting from a monomer. I had
already such a barrel-shaped tetramer structure that I am using as template. Now I am using this tetramer and a dimer from this tetramer placed sufficiantly at optimal distance after avoiding the bad contacts to prepare the hexamer. Only restriction that I need to form such a hexamer is hydrogen bonds between a set of atoms. I am using 54 hbond restraints of which 44 hbonds are already preformed and 10 hbonds are to be formed by the simulation. I am wondering how to decide the force constant to speed up the simulation to achieve the target structure. Please note that I do not need a smooth free energy profile for this as I am interested to prepare the hexamer only that will be used in the final simulation. Here, I am attaching the colvar config file that I am using for the simulation. It seems that the molecules are not moving at all which is likely due to the bad choice of force constant. I am using the initial centers values for this case is the distance between donor and acceptor atom. Can anyone please suggest me an idea how to choose the force constant for my purpose or what parameters to be tuned to speed up this process? Please also point out if I am doing anything wrong in preparing the colvar config file.
Thanking you,
Sincerely,
Prabir

Prabir Khatua
Postdoctoral Research Associate
Department of Chemistry & Biochemistry
University of Oklahoma
Norman, Oklahoma 73019
U. S. A.

--
Prabir Khatua
Postdoctoral Research Associate
Department of Chemistry & Biochemistry
University of Oklahoma
Norman, Oklahoma 73019
U. S. A.
--
Prabir Khatua
Postdoctoral Research Associate
Department of Chemistry & Biochemistry
University of Oklahoma
Norman, Oklahoma 73019
U. S. A.
--
Prabir Khatua
Postdoctoral Research Associate
Department of Chemistry & Biochemistry
University of Oklahoma
Norman, Oklahoma 73019
U. S. A.

This archive was generated by hypermail 2.1.6 : Sat Sep 14 2019 - 23:20:06 CDT