Re: Steered MD along detected routes

From: Johny Telecaster (johnytelecaster_at_gmail.com)
Date: Sat Nov 16 2013 - 10:27:38 CST

Dear Munir,

You investigations are very interesting. From your paper I've understood
that to simulate unbinding is easily that binding (what you've actually do
in your study) But your approach of multi-point MD might be still very
useful.

Little example

-0.178 1.511 2.406 are the started coordinates corresponded to the COM of
my ligand

Supposing that I chose from the predicted dissociation path 4 extra points
corresponded to the turn regions

[-1.443, 2.706, 4.485],
 [0.180, 1.187, 9.484],
[0.402, -2.330, 11.8940],
 [-0.127, -4.221, 17.162]

Here you can see that 5 points (included starting points) are ranged mainly
on Z (increasing Z from protein interior to the surrounding)

No as I understtod 5 directions could not be defined in one conf file so I
should to make 5 subsequent sMD simulations in each of which

SMD on
SMDFile smd_ref.pdb # corresponded to the ligand positioned in the initial
COM xyz
SMDk 5
SMDVel .00001 ;# 10 A/ns = .01 A/ps = .00001 A/fs
SMDDir -1.443, 2.706, 4.485 # corresponded to the 1rst point taken from the
pathway
SMDOutputFreq 100

than the second conf should be

SMD on
SMDFile smd_ref2.pdb # should be taken as the output from the previous run
SMDk 5
SMDVel .00001 ;# 10 A/ns = .01 A/ps = .00001 A/fs
SMDDir 0.180, 1.187, 9.484 # corresponded to the 2nd point taken from the
pathway
SMDOutputFreq 100

etc (overall 5 simulations).

Does such method correct in general ?

My suggestion: I suppose that some problems might be arisen during the PMF
calculations where ~10 windows extracted from the concatenated trajectory
(from those 5 trajectories) will be needed. For example how I specify
colvar precisely (typical its position restrictions on Z) for each window?

Also could some one provide me with the script for analysis of the sMD data
( I'd like to measure force along time coordinate (not position as in the
tutorial).

Many thanks for suggestions,

Johny

2013/11/16 Munir S. Skaf <skaf_at_iqm.unicamp.br>

>
> Dear Johny,
>
> Perhaps you don't need to define your SMD routes precisely along a cuved
> path, but it may
> turn out that a few (say, 3 or 4) turning points on a given pathway are
> sufficient to smoothly
> drive your ligand out of the enzyme.
> You have to make educated guesses to define the turning points.
> Please take a look at Leandro Martínez's work:
>
> J. Phys. Chem. B 2008, 112, 10741–10751
> This multi-point SMD approach preserves the desired physics of the
> force profile.
> Best,
> munir
>
>
>
> On Sat, Nov 16, 2013 at 9:10 AM, Johny Telecaster <
> johnytelecaster_at_gmail.com> wrote:
>
>> Dear NAMD Developers,
>>
>>
>> I have some questions about stereed MD. In particular I'd like to
>> simulate ligand unbinding from the enzyme. Using CAVER Pymol plugin I've
>> detected 3 possible paths inside my protein. Now I'd like to run stereed MD
>> along each of that routes to measure forces affected on the ligand during
>> its motions along each of it. How I could define force directions
>> presicely along CAVER paths? Does it possible to define this pathes as the
>> colvar restrictions? Please provide me with example.
>>
>>
>> Many thanks for the suggestions,
>>
>>
>> Johny T.
>> Scanned and tagged with DSPAM 3.10.2 by Instituto de Quimica - Unicamp
>> !DSPAM:106,5287537b107521489016123!
>
>
>
>
> --
> Munir S. Skaf
> Institute of Chemistry - Cx. P. 6154
> State University of Campinas - UNICAMP
> Campinas - SP 13084-862, Brazil
> Tel. 55 19 3521 3093 / Fax: 3521 3023
>

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