[gmx-users] RE: Re: Binding Energy to Binding affinity (Kd)

[Thomas Schlesier]

You could use 'constraint' pull-mode instead of the 'umbrella' mode. 
Than the distance would change gradually and you won't observe the 
fluctuations in the distance.

greetings
thomas


Am 04.10.2012 16:58, schrieb gmx-users-request at gromacs.org:
> On 10/4/12 10:52 AM, jiang wrote:
>> >Justin Lemkul wrote
>>> >>On 10/2/12 4:39 AM, Du Jiangfeng (BIOCH) wrote:
>>>> >>>Hi Justin,
>>>> >>>
>>>> >>>I used ~20 windows to sample ~2 nm pulling. I notice that the distance
>>>> >>>between the complex being increased during the pulling but not gradually.
>>>> >>>At the distance of 0-1nm, there are 70 snapshots (the distance sometime
>>>> >>>increased sometimes decreased). At the distance of 1-2nm, there are only
>>>> >>>30 snapshots (the distance kept increasing always). At the distance more
>>>> >>>than >3nm, the distance increased as 0.3nm of each snapshot, is it normal
>>>> >>>and reliable?
>>>> >>>
>>> >>
>>> >>I will assume you are using a harmonic potential (umbrella) to do the
>>> >>pulling.
>>> >>In this case, your observations are totally normal.  When two species
>>> >>interact
>>> >>strongly, it is harder to pull them apart, thus the spring extends further
>>> >>to
>>> >>induce a larger force before displacement occurs.  As the restoring forces
>>> >>are
>>> >>overcome, it is easier to move the pulled group through solution, so it
>>> >>makes
>>> >>more steady progress as the molecules are separated.
>> >
>> >
>> >Hi Justin, it is right I am using umbrella pulling. Now here is another
>> >hurdle in front of me: How to select the snapshots for umbrella samples?
>> >Since the distance between two groups went higher or lower at the beginning
>> >of the pulling. For example, during the pulling simulation, the distance
>> >changes like:
>> >0.46 0.42 0.46 0.43	0.44 0.42 0.45 0.44 0.43 0.45 0.44 0.45 0.43 0.44 0.44
>> >0.54 0.52 0.63 0.65 0.72 0.8 0.92 1.2 1.5 (nm) .....
>> >I suppose it doesn't matter which snapshots to be chosen, as long as the
>> >snapshots can indicate a good spacing, the PMF result always should be same,
>> >right?
>> >
> You need reasonable spacing and sufficient sampling in each window to allow for
> proper overlap of the umbrella potentials.
>
> -Justin