NOE restraints with multiple copies of same peptide

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1

Hello -
GROMACS version: 2019
GROMACS modification: No
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I am looking for some guidance on applying NMR NOE restraints. My simulation system contains multiple (20) copies of the same peptide. Take the following example NOE:
ASSI { 72} (( segid A and resid 3 and name HE3 )) (( segid A and resid 1 and name HE3 )) 3.780 0.756 1.256

This indicates the NOE range is 3.024 - 5.036. This leads me think that in the [distance_restaints] for this pair I would set: low = 3.024 and up1 = 5.036. But I have have two questions:

  1. What should I set up2 as? I was thinking to set it at something large (like up2 =20) so the restraint energy stays harmonic
  2. I am confused by what the implication of having multiple copies of the same peptide that are experiencing this restraint is. In the documentation it states:

It is also possible to use ensemble averaging using multiple (protein) molecules. In this case the bounds should be lowered as in:

r1 = = r1∗M**(−1/6)
r2 = r2∗M**(−1/6)

where M is the number of molecules. The GROMACS preprocessor grompp can do this automatically when the appropriate option is given.

Does this mean the values of low and up1 should shift to low=3.024*(20)^(-1/6) = 1.835 and
up1 = 5.036*(20)^(-1/6) = 3.056 ???

What is meant by “grompp can do this automatically when the appropriate option is given”??

Thank you for your help!

Eric

2

Hi,

To do ensemble averaging using multiple peptides (assuming that the peptides are idential) you can set the mdp option disre= ensemble (see more
Molecular dynamics parameters (.mdp options) — GROMACS 2020.5 documentation). This will allow grompp to detect what you want to do

If you have multiple peptides in the system, you have to correct r1 and r2 manually according to the formula (eq 21 in the manual). Note the values of r1 and r2 have to be in nm. (GROMACS uses ‘nm’ as unit for length)

Best regards
Alessandra