[gmx-users] Zn ion as a metal center in a protein: setting distance restraints

[Luca Mollica]

Dear all,

I have tried to simulate my protein-ligand system in water as usual, but my protein has two Zn atoms that
bind 3Cys and 1 His (Zn1) and 4Cys (Zn2). I have browsed the literature and the ML: the most common
suggestion that I had found was the usage of distance restraints in my protein topology file.
After a bit of manual reading, I have set up my table for distance restraints as follows:

[distance restraints]

620  98 1   0   1   0.18 0.30 0.35 1	;Zn1 - His
620 120 1   0   1   0.18 0.30 0.35 1	;Zn1 - Cys1
620 278 1   0   1   0.18 0.30 0.35 1	;Zn1 - Cys2
620 304 1   0   1   0.18 0.30 0.35 1	;Zn1 - Cys3
621 479 1   1   1   0.18 0.30 0.35 1	;Zn2 - Cys4
621 222 1   1   1   0.18 0.30 0.35 1	;Zn2 - Cys5
621 200 1   1   1   0.18 0.30 0.35 1	;Zn2 - Cys6
621 455 1   1   1   0.18 0.30 0.35 1	;Zn2 - Cys7

and the options used in the mdp file were:

disre               =  simple
disre_fc            =  4000
disre_weighting     =  equal


I have noticed that, with respect to the first simulation that I had set up  without distance restraints 
(just a mistake) I do not see my two Zn atoms floating in solution like counterions or water molecules. 
Neverthless, I am not really happy of the result I got: indeed, the second Zn atom (indexd with 1) is 
more or less stable in its coordination pocket (Zn-S distance ~4-5 A), whereas  the first Zn atom 
(indexed with 0) is really strongly bound to Nd1 but it is not in the right coordination, being the 
distance between Zn and Cys S atoms  ~ 7-8 Angstrom.
Do you have any suggestion about how to get an improvement in my simulations ? Moreover, do you think 
that the distance restraints table is badly written and/or does it contain errors ? My desire is to use a 
distance restraints table that allows distance (without penalty) between 1.8 A and 3.5 A, which are the 
same restraints tha have been used for structure determination by NMR (using CYANA).

Thanx a lot for any help

All the best



		Luca

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