Jan-Philip,
Many thanks indeed. Crystal clear now.
Best wishes
George
On Dec 14, 2012, at 6:16 PM, Jan-Philip Gehrcke <jgehrcke.googlemail.com> wrote:
> George,
>
> In this discussion I was missing so far that the force is calculated
> dynamically in each MD time step, from the gradient of the according
> potential.
>
> This means we're dealing with a self-correcting system. Via pulling
> velocity v and the two distance endpoints we define a *desired* linear
> distance-time curve d(t). In each time step, the *actual* distance-time
> state of the system slightly deviates from this curve and a
> 'correctional' force with a certain magnitude and direction is applied
> to the system in order to enforce the desired d(t) relation. Hence, the
> direction of the correctional force may vary from time step to time step.
>
> Then it is obvious that the trajectory of the two restrained atoms still
> is random and that in the final state each atom must be on a spherical
> surface with center=other_atom and radius=target_distance.
>
> Regards,
>
> Jan-Philip
>
>
> On 13.12.2012 16:17, George Tzotzos wrote:
>> Thank you all. Now it's clear.
>>
>> Regards
>>
>> George
>>
>> On Dec 13, 2012, at 3:45 PM, Adrian Roitberg wrote:
>>
>>> Dear all
>>>
>>> I am not sure if I understand Gerrge's diagram correctly, but what seems
>>> to be missing from it is the biomolecule.
>>>
>>> Imagine that you push 'radially', meaning away from the center you
>>> defined. If you now hit a hard wall because a protein residue stands in
>>> the way, you can then move at an angle with ZERO cost for the restraint
>>> (because you are still at the same distance) and find yourself a better
>>> escape route.
>>>
>>> All this fails if you move the restraint too fast or if you use a force
>>> constant that is to high. In that case, you will try to push outwards
>>> regardless of the biomolecule and you can imagine how that would be very
>>> bad...
>>>
>>> adrian
>>>
>>> On 12/13/12 9:41 AM, Jason Swails wrote:
>>>> On Thu, Dec 13, 2012 at 8:54 AM, George Tzotzos <gtzotzos.me.com> wrote:
>>>>
>>>>> Jason,
>>>>>
>>>>> Thank you.
>>>>>
>>>>> You say "Their reference to a sphere is simply that the locus of points
>>>>> that are, say, 10 angstroms away from a certain point make up a sphere of
>>>>> radius 10 with that point at the center"
>>>>>
>>>>> This is UNDERSTOOD.
>>>>>
>>>>> Next: "a ligand that is moved 10 Angstroms away from the active site could
>>>>> lie anywhere on the resulting sphere, not necessarily where you 'want it
>>>>> to' or 'think it should' land."
>>>>>
>>>>> This is also UNDERSTOOD as it stands. The next sentence though is not.
>>>>> Apologies for my lack of "vision".
>>>>>
>>>>> "while the applied force has a well-defined direction (as any vector in
>>>>> this case must have), the 'escape path' of the ligand does not".
>>>>>
>>>>> Do you mean that although the force is applied in one direction the ligand
>>>>> may escape according to the diagram below?
>>>>>
>>>> The force always has a direction. It must, otherwise, how would you know
>>>> in what direction to move the particle that time step? However, the
>>>> direction of the steering force could be any direction away from the
>>>> binding site. Consider a 2-particle system with that biasing force. The
>>>> direction of the force would simply push the particles apart along the
>>>> initial displacement vector. As a result, the direction of travel (apart
>>>> from being "away" from the binding pocket) depends strongly on the initial
>>>> conditions and environment.
>>>>
>>>> HTH,
>>>> Jason
>>>>
>>>
>>> --
>>> Dr. Adrian E. Roitberg
>>> Professor
>>> Quantum Theory Project, Department of Chemistry
>>> University of Florida
>>> roitberg.ufl.edu
>>>
>>>
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Received on Fri Dec 14 2012 - 11:30:03 PST
