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

[Justin Lemkul]

On 8/7/16 7:33 PM, Billy Williams-Noonan wrote:
> Hi All,
>
> Just an update.  I regenerated the topology for the linear peptide with the
> ATB and found myself with similar problems.
>
> Will this pull until the Z-component of the COM distance is 3.2 nm and hold
> it in place?
>
> 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        =  *3.20*
> pull_coord1-start       = no
>
> pull_print-components   = yes
>
> pull_nstxout = 10
> pull_nstfout = 1
>
> Is this doing what I think it is doing?  Because it has worked for every
> other example I have been using.
>

I just posted in a similar thread about this - in effect, yes, but if your 
starting distance deviates a lot from 3.2, the initial forces are going to be 
massive and potentially unstable.

-Justin

> Best regards,
>
> Billy
>
> On 4 August 2016 at 17:28, Billy Williams-Noonan <
> billy.williams-noonan at monash.edu> wrote:
>
>> 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
>>
>> *LinkedIn Profile
>> <http://www.linkedin.com/profile/preview?locale=en_US&trk=prof-0-sb-preview-primary-button>
>> **|*   +61420 382 557
>>
>> Monash Institute for Pharmaceutical Sciences ( *MIPS* )
>> Royal Parade, Parkville, 3052
>>
>>
>
>

-- 
==================================================

Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

==================================================