[gmx-users] Re: g_wham problem with negative COM differences

[Thomas Schlesier]

Anni Kauko wrote:
 > >
 > >     Date: Wed, 11 Apr 2012 08:38:05 -0400
 > >     From: "Justin A. Lemkul" <jalemkul at vt.edu <mailto:jalemkul at vt.edu>>
 > >     Subject: Re: [gmx-users] g_wham problem with negative COM 
differences
 > >     To: Discussion list for GROMACS users <gmx-users at gromacs.org
 > >     <mailto:gmx-users at gromacs.org>>
 > >     Message-ID: <4F857B2D.3050100 at vt.edu 
<mailto:4F857B2D.3050100 at vt.edu>>
 > >     Content-Type: text/plain; charset=ISO-8859-1; format=flowed
 > >
 > >
 > >
 > >     Anni Kauko wrote:
 > >      > Hi!
 > >      >
 > >      > I try to perform pmf calculations for case where a peptide 
shifts
 > >      > through the membrane. My COM differences should vary from 2.3 to
 > >     -2.5.
 > >      >
 > >      > My problem is that g_wham plots negative COM difference as they
 > >     would be
 > >      > positive.  In pullx-files the COM differences are treated 
correctly
 > >      > (look below). My peptide is not symmetric, so profile curves 
are not
 > >      > symmetric, so loosing the sign for COM difference screws my 
profile
 > >      > curve completely.
 > >      >
 > >      > I did not manage to find any pre-existing answers to this 
problem
 > >     from
 > >      > internet.
 > >      >
 > >      > First datalines from pullx files:
 > >      > (sorry for strange file names...)
 > >      >
 > >      > pull_umbr_0.xvg:
 > >      > 0.0000  6.26031 2.27369
 > >      >
 > >      > pullz_umbr_23.xvg:
 > >      > 0.0000  6.09702 0.0233141
 > >      >
 > >      > pullz_umbr_50.xvg:
 > >      > 0.0000  6.02097 -2.50088
 > >      >
 > >      > g_wham command:
 > >      > g_wham -b 5000 -it tpr_files.dat  -ix pullz_files.dat -o
 > >      > profile_test.xvg -hist histo_test.xvg  -unit kCal
 > >      >
 > >      > My pull code:
 > >      >
 > >      > pull            = umbrella
 > >      > pull_geometry   = distance
 > >      > pull_dim        = N N Y
 > >      > pull_start      = yes
 > >      > pull_ngroups    = 1
 > >      > pull_group0     = POPC_POPS         ; reference group is bilayer
 > >      > pull_group1     = C-alpha_&_r_92-94 ; group that is actually 
pulled
 > >      > pull_init1      = 0
 > >      > pull_rate1      = 0.0
 > >      > pull_k1         = 1000     ; kJ mol-1 nm-2
 > >      >
 > >
 > >     Your problem stems from the use of "distance" geometry.  This 
method
 > >     assumes the
 > >     sign along the reaction coordinate does not change, i.e. always
 > >     positive or
 > >     always negative.  If the sign changes, this simple method fails.
 > >      You should be
 > >     using something like "position" to allow for a vector to be
 > >     specified.  Perhaps
 > >     you can reconstruct the PMF by separately analyzing the positive
 > >     restraint
 > >     distances and negative restraint distances (note here that
 > >     "distance" really
 > >     refers to a vector quantity, and thus it can have a sign), or
 > >     otherwise create
 > >     new .tpr files using "position" geometry, though I don't know if
 > >     g_wham will
 > >     accept them or not.
 > >
 > >     -Justin
 > >
 > >     --
 > >     ========================================
 > >
 > >     Justin A. Lemkul
 > >     Ph.D. Candidate
 > >     ICTAS Doctoral Scholar
 > >     MILES-IGERT Trainee
 > >     Department of Biochemistry
 > >     Virginia Tech
 > >     Blacksburg, VA
 > >     jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
 > >     <tel:%28540%29%20231-9080>
 > >     http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin
 > >
 > >     ========================================
 > >
 > >
 > > Thank's!
 > >
 > > I managed to solve my g_wham problem by doing two things:
 > >
 > > 1. New tpr-files with proper pull code for g_wham.
 > > 2. I also needed to modify signs of pullf values: If value for pullx
 > > distance was negative, I reversed the sign of corresponding pullf 
value.
 > > I did that by my own script.
 > >
 > > The new pull code:
 > >
 > > ; Pull code
 > >
 > > pull            = umbrella
 > > pull_geometry   = direction
 > > pull_vec1       = 0 0 1
 > > pull_start      = yes
 > > pull_ngroups    = 1
 > > pull_group0     = POPC_POPS         ; reference group is bilayer
 > > pull_group1     = C-alpha_&_r_92-94 ; group that is actually pulled
 > > pull_init1      = 0
 > > pull_rate1      = 0.0
 > > pull_k1         = 1000     ; kJ mol-1 nm-2
 > >
 > > I am little bit confuced, why I needed to tweak signes of pullf 
values.
 > > But like that I got the curve that resembles two half curve made for
 > > positive and negative pullx distances separately. That curve also 
makes
 > > sense from biochemical point of view.
 > >
 >Such changes do not seem appropriate to me.  If you change the sign of 
 >the
 >pulling force, you change the implication of what that value means. 
 >What
 >happens if you run your simulations with the new (more appropriate) 
 >.mdp file?
 >Do the forces have the same magnitude, but opposite sign?

I don't think that the problem is so easy fixed. I had with another 
person about a month ago a lengthy discussion on the list.

The problem is the following:
If you use 'distance' as pull_geometry the position of the minimum of 
the umbrella potential is determined by the vector connecting the ref- 
and pulled group, but there is no information about the direction.

Assume this (1D):
reference particle at origin (0)
minimum of umbrella potential (1) - via pull_init1 = 1
pulled particle at (0.5)
-> force acting of pulled particle 0.5*k
-> everything ok
--------------------------------------------------------
we look later and pulled particle moved to (-0.5)
since we are in the same umbrella sampling windows the umbrella 
potential minimum should still be at (1) -> force acting would be 1.5*k
(this would be right if we had direction as the pull_geometry)
BUT:
we have pull_geometry=distance
-> minimum of umbrella potential is now at (-1)
(why is this: from ref seen pull-group is now in the negative direction 
-> pull_init tells use that we should go along this vector the distance 
1 -> new position is now (-1))
-> force acting is now -0.5*k
which is wrong (meaning physical not sensible)
ok, the force is right (from the algorithm standpoint), but the fact 
that our minimum of the umbrella potential jumps around during the 
sampling screws everything
--------------------------------------------------------------

hope you get the idea about the origin of problem

greetings
thomas


 > > -Anni
 > >
 > > PS. Thank's for your excellent tutorials. They have been indispensable
 > > help for me to get started with gromacs!
 >Glad to hear it :)
 >
 >-Justin