From: Aron Broom (broomsday_at_gmail.com)
Date: Fri Apr 17 2015 - 18:00:09 CDT
just a quick extra note, whenever there isn't enough simulation time for
any of these methods, you will always get an energy that is biased towards
making whatever your starting conditions are look more favourable than they
ought to be.
On Fri, Apr 17, 2015 at 6:57 PM, Aron Broom <broomsday_at_gmail.com> wrote:
> There are certainly a large number of options for something like this:
> umbrella sampling (as Josh mentioned), ABF, Metadynamics, and so forth.
> But, to get a reasonable result, you'll need a very long total simulation
> time. This is already a difficult problem for a simple ligand binding to a
> protein, but protein-protein binding involves a lot more interactions and
> moving parts. Based on what you've written, it seems like the binding
> would have been completely broken by about 10ns into the simulation? I
> would suggest, if you want to keep trying SMD, that you slow the pulling
> velocity substantially, that is 10-100 fold, such that you capture the
> relevant motion over the course of at least 100ns.
>
> If you are thinking about something like umbrella sampling, I suggest
> doing a search for NAMD and ligand binding with the authors: Gumbart, Roux
> and Chipot. That will give you the full framework for how to get an
> accurate energy with the least simulation time. Note that such a task
> isn't trivial yet, it requires a lot of human time investment and
> understanding.
>
> On Fri, Apr 17, 2015 at 6:43 PM, Josh Vermaas <vermaas2_at_illinois.edu>
> wrote:
>
>> Hi Chola,
>>
>> The way I like doing this is to use the collective variables module to do
>> umbrella sampling along some reaction coordinate that describes the binding
>> process (usually based on coordnum, but unfortunately its broken in the
>> released binaries of 2.10). Usually this doesn't deform the protein like an
>> SMD pull would, since the weakest contacts would break first, and the
>> protein is free to do what it wants, so long as the coordination number
>> between the two parts is restrained.
>>
>> -Josh
>>
>>
>> On 04/17/2015 05:26 PM, Chola Regmi wrote:
>>
>> Dear all,
>> I used SMD simulation to calculate the PMF between two protein domains.
>> I oriented the domains
>> along the z-axis and applied the force in one domains using backbone
>> atoms and kept other domain fixed at its COM of backbone atoms using
>> "fixedAtoms on" command. I found the PMF very high as compare to
>> experimental value. When I observed the trajectories I found that not all
>> system of protein uniformly moved along z but the weak interaction region
>> of protein moves faster than strong keeping COM motion correct with
>> structural deformation. For me this gave the information about weak and
>> strong binding sites but not the true PMF. I used spring constant 15
>> kcal/mol/A^2 and pulling velocity 1A/ns. Can anyone suggest the best way to
>> calculate PMF between protein protein domains using NAMD.
>>
>> Following is the extra-parameter section I used in NVT ensemble.
>>
>> #####################################################
>> fixedAtoms on
>> fixedAtomsFile ref.pdb
>> fixedAtomsCol B
>> #######################################################
>> SMD on
>> SMDFile ref.pdb
>> SMDk 15
>> SMDVel 0.000002 ;#velocity/2fs
>> SMDDir 0 0 -1 ;#pulling direction -z
>> SMDOutputFreq 50
>> ##########################################################
>>
>> Thank you.
>>
>> Chola Regmi
>> Virginia Tech
>>
>>
>>
>
>
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo
>
-- Aron Broom M.Sc PhD Student Department of Chemistry University of Waterloo
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