Heparin polymer psf generation error

HADDOCK
1

Hi,

I am trying to dock heparin against my protein using NMR derived AIRs. I have tried to do this on the HADDOCK2.4 webserver but heparin blows apart. I have installed cns1.3 and HADDOCK2.4 on my local machine and they appear to be working correctly. I have defined heparin as 3 units (a disaccharide unit for the reducing end, a repeating disaccharide unit for the polymer length and an oxidising end disaccharide unit). I have used PRODRG to create topology and parameter files and have merged these. I created the following link file as with the .top and .param, placed these in the HADDOCK toppar dir:

link GL14 head - * tail + * end

With this link file it runs but then in the output dock, the heparin disaccharide units have again blown apart. However, if I instead run it without the wildcards:

link GL14 head - NHO tail + CHO end
link GL14 head - CHO tail + CHO end
link GL14 head - CHO tail + THO end

I get the following error message below. So I am sure this is to do with my files but not quite sure what. Any advice will be very gratefully received - and I can post/send topology/param/pdb files as well if requested

thanks

J

PDB_FILE1 /Users/jimmy-imac/Desktop/haddock/hep/md1_A.pdb
AMBIG_TBL /Users/jimmy-imac/Desktop/haddock/hep/site1/site1_air.tbl
PROJECT_DIR /Users/jimmy-imac/Desktop/haddock/hep/site1
PDB_FILE2 /Users/jimmy-imac/Desktop/haddock/hep/heparin10_B.pdb
looking for existing files
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.pdb…
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.psf…
waterdock false
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.pdb…
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.psf…
waiting for the psf files…
…
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.pdb…
waiting for /Users/jimmy-imac/Desktop/haddock/hep/site1/run1/begin/heparin10_B.psf…
Error in the topology generation: prot_psf_mol2 could not be created
=> HADDOCK stopped

2

Hi J

For the server, you would have to define heparin as a single residue, with unique atom names, e.g. add a number to each atom name to reflect the unit to which it belongs (we have docked in the past heparin actually).

As for your local version, there must be errors reported at the topology generation step for heparin.
Check the out files in the begin directory.

3

Hi,

thanks fro yah guidance - yes I had forgotten to add topology and parameter descriptions for the link between the disaccharide unites. it is working perfectly now on my local machine. Just one final question - how do I get the clustering to work on just the ligand e.g. chain B; rather than the whole complex?

thanks

James

4

Clustering on the ligand only doesn’t make much sense…

You get very different docking solutions clustering together…

5

yes I see - I will tighten the overall RMSD for clustering instead.

thanks for all of the help

J

6

You might also consider using FCC as clustering method.

And indeed play a bit with the clustering cutoff to optimise it for your case.