Re: [AMBER] Conformation search speed increase with Cartesian restraints

From: Liao <>
Date: Thu, 20 May 2021 05:02:32 +0800

Dear Charo,
Thanks for your answers and comments,
Talking about gamma_ln values, for the past few months I am still trying to gradually digest the effect of its different values on the speed conformation search. The reason why I used 0.01 is because based on this paper (, they reported the fastest conformation search using the smallest friction coefficient, although that is for implicit solvent. Why would explicit solvent be different? The water molecules may slow things down for all values of gamma_ln, but it shouldn't change the trend from what I think?

Going back to an old thread from 2015 (, the paper suggested by Dave (Langevin dynamics of peptides: The frictional dependence of isomerization rates of N-actylananyl-N'-methylamide ) I had carefuly read, for their small system of 12 atoms they tested, it did not have solvent in it as I understood. They concluded gamma_ln=2 gives the fastest conformation change, based on equilibrium population and time to equilibrium. Although when they change the analysis criteria for calculation of the reaction rate to simple counting of barrier crossing events, one that considers recoils (product moving back to reactant?), it is 0.01 that is fastest. On the marco-level, kinetics definitely should be change in reactant/product population over unit time, but on the microscopic level, maybe there's a broader definition?

As for the internal distance restraints I was talking about, what I mean is that I either use Cartesian restraints to hold the Zinc and its neighboring residues fixed; or I apply a distance restraint to keep the Zinc atom at a fixed distance from its neighboring sulfurs. So the same groups are being held in the two scenarios, just in a different way.

Sender:Charo del Genio <>
Sent At:2021 May 19 (Wed.) 12:26
Recipient:AMBER Mailing List <>
Subject:Re: [AMBER] Conformation search speed increase with Cartesian restraints

On 19/05/2021 04:41, Liao wrote:
> Dear Amber community,
> A feature I found in my simulation these few days was that when I applied Cartesian restraints (ntr=1) to part of my protein (e.g. terminal residues or Zinc finger so that the zinc ion doesn’t fly out), the flexibility of this protein itself, and also movement of another bound protein, apparently increases. When I change the restraints into internal distance restraints (nmropt=1) for the same region, such increased conformation search speed is gone. Things slow down apparently.
> Why is this happening, my rough guess is that this maybe has to do with the Langevin thermostat; when using absolute restraints, the random forces from the thermostat is not dissipated into translational and rotational motion, therefore it turns into internal energy to make the protein flex around much more.
> I set gamma_ln=0.01 in opc water.
> Is this phenomenon commonly seen, or somewhat seen, by others also? And if so, was the reason what I had speculated? Very curious.

Dear Liao,
 I can't really say what causes the increased motion you see with Cartesian restraints, but I have a few comments nonetheless.

First, if you have a zinc finger, or indeed any other metal coordination centre, I suggest you try and parametrize it, rather than just putting a zinc ion in its vicinity and hoping it stays there.
For this, you can use MCPB together with GAMESS (or GAUSSIAN), which does a pretty good job.

Second, what do you mean exactly by internal distance restraints? Do you mean emap restraints or distance/angle restraints? Either way, it's not surprising that you don't see much conformational
changes in this case, since you are quite literally restraining the local or mid-range geometry of your molecule.

Finally, I feel that gamma_ln=0.01 may be a bit low for explicit-solvent simulations. Of course, the optimal value of many parameters depends on the system, but in your case I would probably use a
gamma_ln of the order of 2.0.



Dr. Charo I. del Genio
Senior Lecturer in Statistical Physics
Applied Mathematics Research Centre (AMRC)
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Received on Wed May 19 2021 - 14:30:02 PDT
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