[gmx-users] Re: umbrella sampling for two polymer interaction

[gromacs query]

Dear Thomas,

Thanks a lot again for great reply. Please clarify this also,

>> If one uses only 'Y N N' B would only move along the x-axis due to the
pull, but could move freely in the yz-plane
>>You never want to use the pull-code and 'pull_dim = N N N'
>>This would mean that there is no force acting between your two groups.
Then one could have skipped using the pull-code...

So keeping Y N N will allow free movement in yz plane. So if I want A B to
move freely in xyz but just keep them separated by some distance with
spring const (just like two balloons tied to each other flying in air).
Sorry confused. In AMBER I remember I did once methane-methane interaction,
just distance based umbrella sampling. But there I did not provide any
direction. So should it not be N N N in Gromacs if I want to allow them
freely move in xyz.

thanks,



On Fri, May 31, 2013 at 8:53 PM, Thomas Schlesier <schlesi at uni-mainz.de>wrote:

> For comments to your questions see below.
>
> More general: (somewhat longer than i wanted. Hope you find some answers
> here)
>
> Imagine two interacting particles A and B which are alinged to the x-axis.
> We take A as the reference group, B as pulled group and put the origin of
> the umbrella potential on top of B (pull_start=yes).
> Simulation starts -> A and B moves.
> Pull-code step: From A we calculate the new position of the umbrella
> potential, this is unequal to B, since B moved and our reference point move.
> Now we have a force acting on B, 'pull_dim' controls in which directions
> the force acts. With 'Y Y Y' B is pulled towards the origin of the umbrella
> potential (and with this to the position it should have relative to A).
> If one uses only 'Y N N' B would only move along the x-axis due to the
> pull, but could move freely in the yz-plane. In the end one would get a
> structure where A and B have the right distance in the x-axis but are miles
> away from each other in the yz-plane.
>
> Now imagine we pull B away from A. Since MD simulations normally separete
> the movement of the center of mass of the system, it would look like A and
> B would move away from a middle point.
>
> (Interchanging A and B should give the same results).
>
>
> Think in your case (doing umbrella sampling) the mdp-file you suggested
> would be most appropiate (with 'pull_start=yes' and 'pull_ngroups=1'). This
> gives you a potential which fixes the distance between the two proteins.
> One thing you should be aware is that if you restrain the distance in 3d,
> you have to account for entropic effects (see also the GROMACS manual). If
> you restrain the system only in one direction, these don't arise. Think
> this is the reason why one sees some work with umbrella sampling were the
> restraint works only in one direction.
>
>
> Am 31.05.2013 17:20, schrieb gmx-users-request at gromacs.org:
>
>  Dear Thomas,
>>
>> Thanks a lot for your time and nice explanation. I was not able to get
>> specially the pull_start flag but now its quite clear.
>>
>> I feel sorry, that should be pull_dim = N N N in my case. Also I will be
>> much thankful if you please can help me to make understand following:
>>
>
> STOP!!!
> You never want to use the pull-code and 'pull_dim = N N N'
> This would mean that there is no force acting between your two groups.
> Then one could have skipped using the pull-code...
>
>
>
>> 1)
>>
>>> >>If you do a pulling simulation, there can be reason for chosing the
>>>>
>>> groups (protein = reference , ligand = pulled group, since we want to
>> pull
>> it away)
>>
>> This indeed is correct but I am not able to get depth of this. I mean to
>> say lets keep ligand as a reference and protein as pulled group then yes
>> it
>> sounds stupid but I am not able to provide a reason myself why we can not
>> keep ligand as reference and pull protein rather !!
>>
>
> Think this setup should also work. For some simple systems i imagine it
> should give identical results.
> For complex system i would also think so. But i can't comment on this with
> actual expirience. The dimer systems which i investigated were symmetric...
>
>
>
>
>>
>> 2)
>>
>>  > >3) And also what should be pull_ngroups because if there is no
>>>>
>>>>> >> >reference group then it should be 2
>>>>>
>>>> >>
>>>>
>>> >Better use a reference group -> pull_ngroups = 1
>>>
>> You don't want to pull in absolute coordinates, when your system can
>> rotate..
>>
>> I am not able to understand this part. Can you please provide some example
>> so that it makes easier to understand this
>>
>
> Imagine only a single protein which you want to unfold. In an equilibrium
> simulation the protein can freely rotate in the box. If we use the
> N-terminus as the reference group and the C-terminus a the pulled group,
> the origin of the umbrella potential will always be updated and will
> account for movement of the N-terminus (reference group).
> If one would pull in absolute coordinates, one would need to give the
> position of the umbrella potential in absolute space. The molecule can
> move, but the origin of the potential will always stay fixed at one place.
> Think in the end this would be equal to an position restraint of said group.
> If one would want to restrain the distance of two groups in such a way,
> one would need two umbrella potentials. But since these would be equal to
> two position restraints, there would be no coupling between the two. I
> mean, if both groups move around but would have the same distance it should
> be ok since the distance is fine. But both umbrella potential would pull
> each group back to the initial position.
>
>
>
>>
>> Much thanks again,
>>
>>
>> regards,
>> Jiom
>>
>>
>>
>>
>> On Fri, May 31, 2013 at 1:21 PM, Thomas Schlesier<schlesi at uni-mainz.de**
>> >wrote:
>>
>>  >Look also into the manual. But the tutorial is a nice place to start.
>>> >For further comments see below:
>>> >
>>> >
>>> >  Dear Lloyd,
>>>
>>>> >>
>>>> >>I have read that but my system is different
>>>> >>
>>>> >>regards,
>>>> >>
>>>> >>
>>>> >>On Thu, May 30, 2013 at 8:28 PM, lloyd riggs<lloyd.riggs at gmx.ch>
>>>> wrote:
>>>> >>
>>>> >>  >Dear Jiom,
>>>>
>>>>> >>> >
>>>>>> >>> >Look at justines tutorial, there's example pull .mdp.
>>>>>> >>> >
>>>>>> >>> >Stephan Watkins
>>>>>> >>> >
>>>>>>
>>>>> >>>
>>>>>
>>>> >>
>>>>
>>> >  >
>>>
>>>> >>>
>>>>>
>>>>>> >>> >I want to do Umbrella sampling between two different polymers (A
>>>>>> and B)
>>>>>> >>> >interacting with each other with starting configuration
>>>>>> separated by
>>>>>>
>>>>> >>>some
>>>>>
>>>>>> >>> >distance and I am trying to bring them closer.
>>>>>> >>> >
>>>>>> >>> >I have some queries regarding pull inputs: (this is for to run a
>>>>>>
>>>>> >>>umbrella
>>>>>
>>>>>> >>> >sampling at some distance)
>>>>>> >>> >
>>>>>> >>> >pull = umbrella
>>>>>> >>> >pull_geometry = distance
>>>>>> >>> >pull_dim = Y Y Y
>>>>>> >>> >pull_start = ???
>>>>>> >>> >pull_ngroups = 2?
>>>>>> >>> >pull_group0 = polymer_B
>>>>>> >>> >pull_group1 = polymer_A
>>>>>> >>> >pull_init1 = 0
>>>>>> >>> >pull_rate1 = 0.0
>>>>>> >>> >
>>>>>> >>> >
>>>>>> >>> >please suggest for following:
>>>>>> >>> >
>>>>>> >>> >1) pull_dim I have set to Y Y Y: Is this correct I do not want
>>>>>> to make
>>>>>> >>> >it interact with some directional vector
>>>>>>
>>>>> >>>
>>>>>
>>>> >>
>>>>
>>> >I don't really understand the question. If you use 'pull_dim = Y Y Y'
>>> the
>>> >pulling potential acts in all 3 dimensions, if you use 'pull_dim = Y N
>>> N'
>>> >the pulling potential acts only in the X direction and your two groups
>>> an
>>> >move freely in the YZ-plane.
>>> >
>>> >
>>> >  >
>>>
>>>> >>> >2) Which should be group0 or group1, in other words should I pull
>>>>>> both
>>>>>> >>> >together or how I should decide which one should be reference and
>>>>>> >>> >which to be pulled as both are different polymers?
>>>>>>
>>>>> >>>
>>>>>
>>>> >>Depends on what you want to do. Easiest way would be define one
>>>> polymer a
>>>>
>>> >group0/reference group and the other as group1/pulled group. System
>>> >shouldn't care about which polymer is which group.
>>> >If you do a pulling simulation, there can be reason for chosing the
>>> groups
>>> >(protein = reference , ligand = pulled group, since we want to pull it
>>> away)
>>> >
>>> >
>>> >  >
>>>
>>>> >>> >3) And also what should be pull_ngroups because if there is no
>>>>>> >>> >reference group then it should be 2
>>>>>>
>>>>> >>>
>>>>>
>>>> >>Better use a reference group -> pull_ngroups = 1
>>>>
>>> >You don't want to pull in absolute coordinates, when your system can
>>> >rotate...
>>> >
>>> >
>>> >  >
>>>
>>>> >>> >4) I am not able to understand pull_start option with pull_init1.
>>>>>> In
>>>>>> >>> >this case if it is set to yes and 0.0 respectively then does
>>>>>> that mean
>>>>>> >>> >this combination is equivalent to pull_start = No if I just
>>>>>> assume
>>>>>> >>> >pull_init1 does not have any default value (which is 0.0); not
>>>>>> >>> >existing
>>>>>>
>>>>> >>>
>>>>>
>>>> >> From the setup which you have written above:
>>>>
>>> >polymer_B is the reference group. the origin of the pulling potential is
>>> >at 'pull_init1' (a length) along the vector which goes from polymer_B to
>>> >polymer_A (sine you use pull_geometry = distance).
>>> >If you set pull_init1=0 and pull_start=no, polymer_A will crash into
>>> >polymer_B (since the origin of the umbrella potential is directly at the
>>> >center of mass of polymer_B).
>>> >If you set pull_init1=0 and pull_start=yes, GROMACS adds the distance
>>> >between polymer_B and A to pull_init1 (-> so pull_init1 is now greater
>>> than
>>> >0.0). Now the origin of the umbrella potential is at the center of mass
>>> of
>>> >polymer_A. -> A is restrainted to a certian distance of B.
>>> >
>>> >  >
>>>
>>>> >>> >5) Also finally where are upper and lower bounds defined. pull_k1 =
>>>>>> >>> >1000 is harmonic applied to some equilibrium distance value. How
>>>>>> this
>>>>>> >>> >distance is taken by the programme (or it is just the starting
>>>>>> >>> >distance taken between two groups) and what are the ?? values
>>>>>>
>>>>> >>>
>>>>>
>>>>>> >>> >defined. (say in AMBER I define r1,r2,r3,r4; where r2=r3 which is
>>>>>> >>> >assumed equilibrium value and r1 is lower and r4 is upper value
>>>>>> which
>>>>>> >>> >defines shape of potential)
>>>>>>
>>>>> >>>
>>>>>
>>>> >>The umbrella potential is a simple harmonic potential (so no fancy
>>>> stuff
>>>>
>>> >as in AMBER) with
>>> >V = 1/2 k x^2
>>> >where x is the violation of the equilibrium distance.
>>> >For your setup
>>> >V = 1/2 (pull_init1 - distance(B-A))^2
>>> >where distance(B-A) means the distance between both polymers.
>>> >
>>> >
>>> >Greetings
>>> >Thomas
>>>
>>
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