**From:** Jérôme Hénin (*jhenin_at_ifr88.cnrs-mrs.fr*)

**Date:** Wed Nov 23 2011 - 10:41:58 CST

**Next message:**Aron Broom: "Re: Re: Predicting the binding affinity and anion"**Previous message:**Axel Kohlmeyer: "Re: OpenCL and AMD GPUs"**In reply to:**Giacomo Fiorin: "Re: Scaled forces, colvars and harmonic con/restraints"**Next in thread:**Michelle Kuttel: "Re: Scaled forces, colvars and harmonic con/restraints"**Reply:**Michelle Kuttel: "Re: Scaled forces, colvars and harmonic con/restraints"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

Hi guys,

On 23 November 2011 16:28, Giacomo Fiorin <giacomo.fiorin_at_gmail.com> wrote:

*> Hi Michelle. What you describe seems to me that the angle gets stuck into a
*

*> local minimum. This is pretty typical when you minimize. Then when you try
*

*> the next window, you don't get the results you want because your angle is
*

*> stuck.
*

*>
*

*> I would start all windows from the same initial structure and change the
*

*> center of the static restraint, rather than changing it on the fly while you
*

*> minimize. That would be most appropriate for dynamics.
*

I am not sure that will work so well. The problem is more fundamental:

if the potential is corrugated enough that you get stuck in local

minima, then the relaxed scan is always tricky. I run into this once,

and one test I did was to run the scan both ways to see if I sampled

the same conformations - and if not, which one had lower energy.

You could try scanning this angle while doing MD, to give the molecule

a chance to optimize itself beyond the nearest local minima.

Once the "true" minima are identified, you might have to run the scan

in pieces, starting from the properly minimized structures and

sampling the barriers around going both ways. In the worst case, the

landscape is too complex to be sampled like this, then you'd need some

kind of MC search rather than just a torsional scan.

*> On Wed, Nov 23, 2011 at 9:16 AM, Michelle Kuttel <mkuttel_at_cs.uct.ac.za>
*

*> wrote:
*

*>>
*

*>> The plot thickens....
*

*>> After much experimenting, I have finally determined that, for this
*

*>> particular dihedral, the optimal "harmonic" configuration is:
*

*>> harmonic {
*

*>> name scanOmega
*

*>> colvars Omega
*

*>> centers -180
*

*>> targetCenters 180
*

*>> targetNumSteps 500 #these
*

*>> targetNumStages 72 #are the values
*

*>> forceConstant 0.005 # in question
*

*>> }
*

*>> So ,it seems that my previous values were far too "high". However, I
*

*>> still don't understand why, if I increase targetNumStages and
*

*>> targetNumSteps, I need to increase the force constant as well.
*

*>> "targetNumSteps" should just be number of minimization steps at a
*

*>> particular force, surely, and not affect the applied force, right? But it
*

*>> does!
*

Note that the force constant is in unit of kcal/mol/square colvar

unit, where the effective colvar unit is given by the width parameter.

Here, it is 0.5 degrees, which is very small, meaning that a force

constant of 100 is really huge (deviating from the restraint center by

0.5 degrees costs 100 kcal/mol of energy). A looser restraint leaves

more leeway for various degrees of freedom to relax, possibly yielding

a better optimization.

The reason targetNumStages matters is, you may not get trapped in the

same local minima depending on the size of the "hops" in the reference

torsional angle.

Best,

Jerome

*>> The use of "harmonic" to create relaxed energy maps is not documented in
*

*>> the NAMD User Guide, other than the comment:
*

*>> "The harmonic biasing method may be used to enforce fixed or moving
*

*>> restraints, including variants of Steered and Targeted MD. Within energy
*

*>> minimization runs, it allows for restrained minimization, e.g. to calculate
*

*>> relaxed potential energy surfaces.".
*

*>> So, I would really appreciate it if someone can explain this to me.
*

*>> Pretty please?
*

*>> Michelle
*

*>>
*

*>> On 21 Nov 2011, at 12:45 PM, Michelle Kuttel wrote:
*

*>>
*

*>> Hello
*

*>> I am trying to calculate a simple relaxed energy profile for a dihedral
*

*>> angle (this is a simple sanity check - I can compare the profile to one I
*

*>> calculated some time ago in CHARMM).
*

*>> I am using colvars and harmonic restraints to do this. My colvarsConfig
*

*>> file looks like this:
*

*>> ------------------------------------
*

*>> colvarsTrajFrequency 10000
*

*>> colvar {
*

*>> name Omega
*

*>> width 0.5
*

*>> dihedral {
*

*>> group1 {
*

*>> atomnumbers { 7 }
*

*>> }
*

*>> group2 {
*

*>> atomnumbers { 5 }
*

*>> }
*

*>> group3 {
*

*>> atomnumbers { 20 }
*

*>> }
*

*>> group4 {
*

*>> atomnumbers { 21 }
*

*>> }
*

*>> }
*

*>>
*

*>> }
*

*>> harmonic {
*

*>> name scanOmega
*

*>> colvars Omega
*

*>> centers -180
*

*>> targetCenters 180
*

*>> targetNumSteps 10000
*

*>> targetNumStages 36
*

*>> forceConstant 100
*

*>> }
*

*>> ----------------------------
*

*>> In my main file, I then have the line:
*

*>> minimize 370000
*

*>> This works OK (though the energies for the first few stages are a bit
*

*>> high). HOWEVER, when I change "targetNumStages 36" to "targetNumStages 72"
*

*>> and "minimize 370000" to "minimize 730000", suddenly I need a much higher
*

*>> force of 200 for it to work. If I don't increase the force, the omega angle
*

*>> (recorded in the .traj file) "stalls" at -145 degrees. The angle does not
*

*>> rotate further than this on subsequent stages.
*

*>> Why would increasing the number of stages require a higher force? I
*

*>> thought that the width of the omega colvar would still be the same (0.5
*

*>> degrees) and therefore the scaling should be the same?
*

*>> I think that I do not understand the way forces are applied under harmonic
*

*>> restraints and I would really appreciate some insight!
*

*>> Many thanks
*

*>> Michelle
*

*>> ---------------------------------------------
*

*>> Dr Michelle Kuttel
*

*>> Department of Computer Science
*

*>> University of Cape Town
*

*>> Cape Town
*

*>> South Africa
*

*>> mkuttel_at_cs.uct.ac.za
*

*>> PH: +27 21 6505107
*

*>> ---------------------------------------------
*

*>>
*

*>>
*

*>>
*

*>
*

*>
*

**Next message:**Aron Broom: "Re: Re: Predicting the binding affinity and anion"**Previous message:**Axel Kohlmeyer: "Re: OpenCL and AMD GPUs"**In reply to:**Giacomo Fiorin: "Re: Scaled forces, colvars and harmonic con/restraints"**Next in thread:**Michelle Kuttel: "Re: Scaled forces, colvars and harmonic con/restraints"**Reply:**Michelle Kuttel: "Re: Scaled forces, colvars and harmonic con/restraints"**Messages sorted by:**[ date ] [ thread ] [ subject ] [ author ] [ attachment ]

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