Re: SMD and CPT?

From: Gianluca Interlandi (gianluca_at_u.washington.edu)
Date: Fri Feb 09 2007 - 22:50:45 CST

I finally integrated Force versus distance. For my constant velocity
pulling simulation in the NVE I get an energy difference of 342.6966
kcal/Mol between the final and the initial state. By integrating F*d with
xmgrace I get 353.306 kcal/Mol. The force was output every 5000 steps. It
seems to work (+/- 10 kcal/Mol).

Thanks a lot,

           Gianluca

On Fri, 9 Feb 2007, Gianluca Interlandi wrote:

> I'm sending Marcos' answer to my last e-mail to the whole list as many
> people might be interested in our discussion.
>
> Marcos, Thank you very much for your help.
>
> Best,
>
> Gianluca
>
> ---------- Forwarded message ----------
> Date: Fri, 9 Feb 2007 13:43:32 -0600 (CST)
> From: Marcos Sotomayor <sotomayo_at_ks.uiuc.edu>
> To: Gianluca Interlandi <gianluca_at_u.washington.edu>
> Subject: Re: namd-l: SMD and CPT?
>
>
> Dear Gianluca,
>
> Two comments on your plots:
>
> - I see you are using a 2fs time step. Are you using rigid bonds and/or multiple
> time stepping? (I guess you are using rigid bonds and not multiple time stepping
> since the temperature seems to be quite under control, good!)
>
> - Check the energy of your system (TOTAL3 in namd output) and compute the
> difference between the starting value and the final value (due to intrinsic
> fluctuations of the energy you will be off by ~ +/- 10 kcal/mol). Then plot
> Force vs distance (I assume the plot you sent is F vs t). The area under Force
> vs distance (you can integrate F vs d numerically using xmgrace, be sure to use
> the appropriate units) should be similar (not identical since you are applying a
> time dependent force) to the energy difference you computed before. That's a
> good way to check that the simulation is OK in terms of the physics behind it.
>
> The temperature rises at the breaking point because that's when the external
> force starts to do work (F \times d). If you plot the energy of your system,
> likely you will see that increases at the breaking point as well.
>
> Although I feel more comfortable with NVE simulations, do not completely
> disregard your CPT simulation, stiffer springs will give you a lot of large
> fluctuations! Likely that's the reason why you see forces on the order of 1200pN
> and probably you will see something similar in your NVE simulation. Plot F vs t
> and a running average (just like you did for the temperature) to see at what
> level is the force.
>
> Finally, the choice of spring constant is a tough one. AFM people use really
> soft cantilevers, while if you want to get a potential of mean force (PMF) you
> need to use a stiff spring (have a look at Park and Schulten, Journal of
> Chemical Physics, 120:5946-5961, 2004.)
>
> Hope this helps and don't hesitate to contact me again if you have further
> questions.
>
> Regards,
> Marcos
> PS: perhaps you could resend this e-mail (without the attachment) to namd-l,
> since I think many people would benefit from our discussion even without the
> plot.
>
>
> On Fri, 9 Feb 2007, Gianluca Interlandi wrote:
>
> > Dear Marcos,
> >
> > Thanks a lot for your answer and for offering me your help.
> >
> > I have already run a bunch of pulling simulations in the NVE ensemble. I
> > attach a plot of a constant velocity simulation where I'm pulling two
> > proteins apart. At the point of breaking the temperature raises of a few
> > degrees. The force peak is at around 670 pN. Recently, I have started a
> > new simulation of the same system but with a stiffer spring, i.e., 140
> > pN/A instead of 14 pN/A, and in the CPT (Langevin as thermostat and
> > Langevin-Nose Hoover as barostat). After 5 ns the force has reached 1200
> > pN but the two proteins are still bound and the total RMSD is still around
> > 2 A. I started wondering whether this is due to the stiffer spring only or
> > whether CPT has introduced some artifacts. To investigate this I have
> > started a new simulation with exactly the same parameters but in the NVE.
> > The latter simulation has just started so I'm waiting for the results.
> >
> > In any case, now I know that I have to stick with NVE.
> >
> > Many thanks,
> >
> > Gianluca
> >
> > On Fri, 9 Feb 2007, Marcos Sotomayor wrote:
> >
> > >
> > > Actually, I have three reasons to disagree with Sterling.
> > >
> > > 1 - Performing simulations in the NVE ensemble permits you to monitor the
> > > change in energy of your system, and check that it is at least similar to
> > > the
> > > work done by the external applied force (and exactly the same when using
> > > constant forces). I've monitored temperature changes of 0.5 K in simulations
> > > that do not use multiple time stepping, which matches well the work done on
> > > the system by external forces.
> > >
> > > 2 - Algorithms used to control temperature usually are not designed to
> > > handle
> > > systems in which external forces induce motions in a preferred direction.
> > > The
> > > Langevin thermostat for instance, will apply a net (average) zero force to
> > > atoms that do not move on a preferred direction, but likely will introduce
> > > an
> > > artificial viscous drag to atoms that are being pulled. Thus, your force
> > > peaks
> > > will be larger.
> > >
> > > 3 - Some temperature control methods induced center of mass motion, which is
> > > not good when you have fixed reference points like in SMD.
> > >
> > > The best solution is to perform simulations in both ensembles and compare,
> > > focusing on those results that are "ensemble independent".
> > > However, with a water box big enough I suggest to perform SMD simulations in
> > > the NVE ensemble.
> > >
> > > Ginaluca, that's the reason why we performed simulations in the NVE ensemble
> > > in our Structure paper. Let me know if you have more questions, I'll be glad
> > > to discuss them with you.
> > >
> > > Regards,
> > > Marcos
> > >
> > >
> > > On Fri, 9 Feb 2007, Sterling Paramore wrote:
> > >
> > > > I would definitely suggest you do SMD with a thermostat. Otherwise, the
> > > > viscous heating that occurs when you pull on your system will increase the
> > > > temperature. In any real system, the heat produced would be transferred
> > > > to
> > > > the surrounding thermal reservoir. The artificial thermostat is just a
> > > > way
> > > > to model this effect.
> > > >
> > > > -Sterling
> > > >
> > > >
> > > > On Feb 8, 2007, at 11:49 PM, Gianluca Interlandi wrote:
> > > >
> > > > > I have a question concerning steered molecular dynamics simulations
> > > > > (constant force and constant velocity). Is it appropriate to use a
> > > > > thermostat and barostat (CPT) while performing a constant force or
> > > > > constant velocity pulling simulation? I have seen that many people
> > > > > prefer
> > > > > NVE, i.e., no thermostat.
> > > > >
> > > > > I expect my protein to undergo large conformational changes during
> > > > > pulling. Does a thermostat slow down the sequence of events, since part
> > > > > of
> > > > > the applied force is converted into heat?
> > > > >
> > > > > Many thanks,
> > > > >
> > > > > Gianluca
> > > > >
> > > > > -----------------------------------------------------
> > > > > Dr. Gianluca Interlandi gianluca_at_u.washington.edu
> > > > > +1 (206) 685 4435
> > > > > +1 (206) 714 4303
> > > > > http://biocroma.unizh.ch/gianluca/
> > > > >
> > > > > Postdoc at the Department of Bioengineering
> > > > > at the University of Washington, Seattle WA U.S.A.
> > > > > -----------------------------------------------------
> > >
> >
> > -----------------------------------------------------
> > Dr. Gianluca Interlandi gianluca_at_u.washington.edu
> > +1 (206) 685 4435
> > +1 (206) 714 4303
> > http://biocroma.unizh.ch/gianluca/
> >
> > Postdoc at the Department of Bioengineering
> > at the University of Washington, Seattle WA U.S.A.
> > -----------------------------------------------------
>

-----------------------------------------------------
Dr. Gianluca Interlandi gianluca_at_u.washington.edu
                    +1 (206) 685 4435
                    +1 (206) 714 4303
                    http://biocroma.unizh.ch/gianluca/

Postdoc at the Department of Bioengineering
at the University of Washington, Seattle WA U.S.A.
-----------------------------------------------------

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