[gmx-users] Problem with my pull-code or my topology (or both) - help appreciated

[Billy Williams-Noonan]

Hi Gromacs Users,

I have been pulling peptides from two separate proteins (let's call them A
and B) by first taking the crystal structure pose and pulling the ligand to
progressively more distant points from the binding site, and then sampling
at that point.

I first pull the ligand out of the binding site over 400ps with a high
force constant (10000 kJ/mol/nm^2), and then sample at that point with a
lower force constant (1000 kJ/mol/nm^2)

The pull-code I have been using in my .mdp file is this:

*400 ps Pull*

pull                    = yes

pull_ngroups            = 2
pull_ncoords            = 1
pull_coord1-groups      = 1 2
pull_group1_name        = reference_pull_group
pull_group2_name        = Pull_Group
pull_coord1-type        = umbrella
pull_coord1-geometry    = direction
pull_coord1-dim         = N N Y
pull_coord1-k           = 20000
pull_coord1-vec         = 0 0 1
pull_coord1-init        =* pull-distance  *
pull_coord1-start       = no

pull_print-components   = yes

pull_nstxout = 10
pull_nstfout = 1

*20 ns sampling:  *

pull                    = yes

pull_ngroups            = 2
pull_ncoords            = 1
pull_coord1-groups      = 1 2
pull_group1_name        = reference_pull_group
pull_group2_name        = Pull_Group
pull_coord1-type        = umbrella
pull_coord1-geometry    = direction
pull_coord1-dim         = N N Y
;pull_coord1-rate       = 0.00005
pull_coord1-k           = 1000
pull_coord1-vec         = 0 0 1
pull_coord1-init        =  *pull-distance*
pull_coord1-start       = no

pull_print-components   = yes

pull_nstxout = 10
pull_nstfout = 1

This has worked for two ligands binding to A and one ligand binding to B
with varying degrees of agreement with experiment.

However, when I try to move my ligands into position with one
linear-peptide ligand binding to B, the ligand moves to 2.7 nm between the
two pull-group's COM... and then refuses to move further.  The initial COM
pull distance was 1.8 nm, and the final pull distance should be 3.2 nm
between the two pull groups' COM.

A cyclic peptide version of this molecule was pulled from the binding site
successfully and its topology was generated with the ATB. The linear
version of this peptide was generated with gmx pdb2gmx and this is the
*only* difference in the protocol between the two protocols.

So either the pull-code I am using is not doing what I think it is (pulling
at specific distances along the Z-direction) *OR* the topology being
generated by *pdb2gmx* is wrong (but I don't think my input is defective).
However, this would make sense given I am getting a lot of LINCS warnings
at some of my positions...

Specifically:


*WARNING (1):*
*lincs-warnangle can not be larger than 90 degrees, setting it to 90.*

Any help would be appreciated... :)

Best regards,

Billy...

-- 
Billy Noonan*    |    *PhD Student    *|*    Bsci ( *Adv* ), IA Hon

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