Re: Why is SHAKE not being used in typical NAMD simulations ?

From: Peter Freddolino (petefred_at_ks.uiuc.edu)
Date: Sun May 27 2007 - 12:01:30 CDT

I think I'd rephrase that a bit less harshly. SHAKE (or, to be more
accurate, rigidbonds, which usually uses SETTLE) brings benefits (in the
form of a computational speedup) to all calculations, and is probably
fine to use for most of them (as Himanshu pointed out, it's sort of the
industry standard for MD these days). I'm suggesting a couple reasons
that I (and other namd users) don't use it at the same levels as the
rest of the MD community:
-Although there's no clearly demonstrated example of this, the loss of
coupling between high and low frequency modes of motion *could* give
unphysical dynamics
-There's a higher chance of innacuracies in some specific instances,
such as when pressure profiles are important (hence the membrane issue)
-It can be technically inconvenient in some circumstances, such as with
systems >= 1 million atoms with constant pressure simulations

What needs to be kept in mind here is that SHAKE is an approximation,
just like MD itself is an approximation. When used appropriately it can
be beneficial (in terms of simulation times), but if applied
inappropriately it will lead to problems. As illustrated by the variety
of successes in the larger MD community with using such techniques,
*most* MD simulations are suitable for this approximation. A few cases
(such as those highlighted above) may not be; also, unlike some other
approximations, the potential time savings are not order of magnitude
level, but rather on the order of 15-20%. I'm fairly certain that most
of the MD community would view even this analysis as overly cautious,
and it well may be. The best advice I can give is the same as what I did
earlier: try some test runs on your simulation with and without
rigidbonds if you have any doubts. For more run-of-the-mill simulations
you may see people avoiding rigidbonds simply out of caution. To be
frank, a lot of very smart people in MD use SHAKE for everything, and
are probably correct to do so. I'd be very interested to see a good,
in-depth analysis of the effects of SHAKE on some of the potential
trouble cases, such as a large, long timescale membrane protein
simulation; having not had the time to do this myself, nor seen it in
the literature, I avoid rigidbonds in these cases. These should *not* be
taken as hard rules; I'm just giving my $0.02.

Peter

L. Michel Espinoza-Fonseca wrote:
> Very interesting. So basically you're suggesting (based on your own
> experience) that SHAKE might bring some benefits when it comes to
> simulate small systems (i.e., a peptide) for very long timescale
> (i.e., more than 100 ns), but not when you simulate very big systems,
> or those including a membrane. Could you add any additional rationale
> for such selection?
>
> Cheers,
>
> Michel
>
> 2007/5/25, Peter Freddolino <petefred_at_ks.uiuc.edu>:
>> Hi Himanshu,
>>
>> I think there are several reasons for this; some might be considered
>> "good" and some not. First, I'd like to clarify something. A bit earlier
>> you said
>>
>> I am hoping some of the developers will
>> be able to tell us why SHAKE is not recommended in NAMD, while it is in
>> other programs?
>>
>>
>> The issue is not that SHAKE is not recommended in NAMD; it is just as
>> advisable in NAMD as in any of the other common MD programs. Please
>> note, also, that the NAMD "developers" and "users" are mostly disjoint
>> sets; it isn't the developers deciding not to use SHAKE, but the users.
>> The issue is just that people in that people in the NAMD community (and,
>> in particular, the KS group) tend to be those that avoid using SHAKE for
>> most applications. This is in large part due to lingering concerns about
>> coupling of different frequency modes of motion (as pointed out by Ana)
>> and pressure profile calculations (see, e.g., JCC 121:8611); this
>> concern is particularly acute within the NAMD community because people
>> tend to do large simulations, frequently containing membranes, and have
>> not yet been adequately convinced that for these applications no
>> pathologies with SHAKE will occur to make it worthwhile using SHAKE for
>> a 15% speedup. SHAKE convergence can also be problematic when using very
>> large systems in constant pressure simulations, which (again) is fairly
>> common in the NAMD community. The speedup from SHAKE also gets less
>> impressive as more processors are used.
>>
>> Some part of this difference is also due to institutional memory; I have
>> no doubt that there are a lot of simulations done without rigid bonds
>> even where they would be fine, because of the concerns highlighted
>> above, and the fact that people in the NAMD community tend to put more
>> stock in those concerns (even in cases where they may not be valid) and
>> choose to err on the side of caution. I know for my own research, I'm
>> using SHAKE in some simulations (particularly those involving long
>> timescale exploration of relatively small systems) but not others (those
>> where I have a membrane or other concerns about the pressure, or very
>> large simulations).
>>
>> You're absolutely correct that SHAKE is quite widely used in
>> biomolecular simulations, and is well tested for most of these
>> applications. Whether or not SHAKE should be applied to any given
>> simulation comes down to personal preference, and an evaluation of
>> whether or not the specific places where it *could* in principle cause
>> trouble are important to your case (preferably including some short
>> simulations of your system with and without SHAKE). I know that people
>> around here are starting to test and use SHAKE a bit more; I think the
>> main reason it isn't used more widely is that the speed improvements
>> aren't, say, on the order of 2x, and for a lot of systems SHAKE doesn't
>> seem worth the risk (that some artifact might appear) or hassle (of
>> running a comparison simulation). Please note that I'm not being
>> cavalier about computing time: a 15% speedup seems much less worthwhile
>> if it costs you 10% more simulation (without rigidbonds, for comparison
>> purposes) or 100% of your simulation (if some sort of problem occurs).
>>
>> Peter
>>
>> Himanshu Khandelia wrote:
>> > It is not entirely true that people shy away from SHAKE. All typical
>> > biomolecular MD simulations use SHAKE very widely, except those
>> > implemented in NAMD. So people do shy away from SHAKE, but only
>> when using
>> > NAMD.
>> >
>> > ----------------------------
>> > Himanshu Khandelia, PhD
>> > Research Assistant Professor (Postdoc)
>> > MEMPHYS, Center for Membrane Physics: www.memphys.sdu.dk
>> > University of Southern Denmark (SDU)
>> > Odense M 5230, Denmark
>> >
>> > Phone: +4565503510
>> > email: hkhandel_at_memphys.sdu.dk
>> > WWW: www.memphys.sdu.dk/~hkhandel
>> > -----------------------------
>> >
>> >
>> >
>> > On Thu, 24 May 2007, Ana Celia Araujo Vila Verde wrote:
>> >
>> >
>> >> Here's my two cents about this issue,
>> >>
>> >> There's a physical reason why people shy away from SHAKE, in
>> particular
>> >> when very interested in getting accurate dynamics: slow and fast
>> >> vibrational modes "talk" to each other, and fast modes may influence
>> >> slow modes. See Baysal, C., et al., Molecular dynamics analysis of
>> >> coupling between librational motions and isomeric jumps in chain
>> >> molecules. Macromolecules, 1996. 29(7): p. 2510-2514.
>> >>
>> >> Getting rid of fast modes by using SHAKE can thus have unexpected
>> >> outcomes in a simulation. So, I'd be comfortable using SHAKE for
>> >> Equilibration in most situations, but I'd evaluate carefully
>> whether the
>> >> 15-20% gains in simulation time are worth the extra uncertainty for
>> >> actual runs. Normally, whether I use SHAKE or not depends on the
>> >> problem I'm studying. If I do use SHAKE, I normally run a comparison
>> >> simulation without it and compare the results to make sure no
>> >> significant differences occur. Most of the time, however, I find the
>> >> extra hassle of running that comparison simulation to be a big
>> pain and
>> >> not worth it for a 15% gain, so I just don't use SHAKE...
>> >>
>> >> I hope this helps,
>> >>
>> >> Ana
>> >>
>> >>
>> >>
>> >> _________________________________
>> >> Ana CÚlia Ara˙jo Vila Verde
>> >> Penn State University
>> >> Department of Chemical Engineering
>> >> Fenske Laboratory
>> >> University Park, PA 16802
>> >> USA
>> >>
>> >>
>> >> Phone: +(1) (814) 863-2879
>> >> Fax: +(1) (814) 865-7846
>> >> avilaverde_at_engr.psu.edu
>> >> http://www.che.psu.edu/Faculty/JMaranas/group/avv.html
>> >> http://www.gfct.fisica.uminho.pt/Members/acvv
>> >> _________________________________
>> >>
>> >>
>> >>
>> >> -----Original Message-----
>> >> From: owner-namd-l_at_ks.uiuc.edu [mailto:owner-namd-l_at_ks.uiuc.edu]
>> On Behalf Of Himanshu Khandelia
>> >> Sent: Thursday, May 24, 2007 9:47 AM
>> >> To: Gianluca Interlandi
>> >> Cc: namd-l_at_ks.uiuc.edu
>> >> Subject: Re: namd-l: Why is SHAKE not being used in typical NAMD
>> simulations ?
>> >>
>> >>
>> >> Please note that this post is not about using multiple time
>> stepping, and
>> >> energy drifts. It is about SHAKE. I am hoping some of the
>> developers will
>> >> be able to tell us why SHAKE is not recommended in NAMD, while it
>> is in
>> >> other programs ?
>> >>
>> >> ----------------------------
>> >> Himanshu Khandelia, PhD
>> >> Research Assistant Professor (Postdoc)
>> >> MEMPHYS, Center for Membrane Physics: www.memphys.sdu.dk
>> University of Southern Denmark (SDU) Odense M 5230, Denmark
>> >>
>> >> Phone: +4565503510
>> >> email: hkhandel_at_memphys.sdu.dk
>> >> WWW: www.memphys.sdu.dk/~hkhandel
>> >> -----------------------------
>> >>
>> >>
>> >>
>> >> On Wed, 23 May 2007, Gianluca Interlandi wrote:
>> >>
>> >>
>> >>> There have been already discussions in the NAMD list about the
>> use of
>> >>> different timesteps. In particular, it seems that the use of a multi
>> >>> stepping algorithm seems to cause an energy drift:
>> >>>
>> >>> http://www.ks.uiuc.edu/~sotomayo/private/answer.html
>> >>>
>> >>> http://www.ks.uiuc.edu/Research/namd/mailing_list/namd-l/5385.html
>> >>>
>> >>> Usually, the conservation of energy is used as a "quality
>> control" for
>> >>> the
>> >>> algorithm and timestep used. Thus if you are concerned about
>> whether the
>> >>> chosen timestep is good or not the first thing to do would be to
>> check
>> >>> whether the energy and temperature are conserved.
>> >>>
>> >>> Gianluca
>> >>>
>> >>> On Wed, 23 May 2007, L. Michel Espinoza-Fonseca wrote:
>> >>>
>> >>>
>> >>>> Note: I mentioned this thing about being reliable enough because
>> >>>> others have told me that, so I just said what I was told by my
>> >>>> colleagues, and it doesn't represent my own view :).
>> >>>>
>> >>>> 2007/5/23, Eric Cyr <ericcyr_at_uiuc.edu>:
>> >>>>
>> >>>>> What is meant by "not reliable enough"? I can think of a couple of
>> >>>>> things this could mean.
>> >>>>>
>> >>>>> Eric
>> >>>>>
>> >>>>> On 5/23/07, L. Michel Espinoza-Fonseca <mef_at_ddt.biochem.umn.edu>
>> >>>>> wrote:
>> >>>>>
>> >>>>>> I myself have asked this question before. My answer (as before)
>> >>>>>> is no idea. Perhaps some people think that SHAKE and MTS schemes
>> >>>>>> are not reliable enough (at least this is what some colleagues
>> >>>>>> have told me before).
>> >>>>>>
>> >>>>>> Cheers,
>> >>>>>> Michel
>> >>>>>>
>> >>>>>> 2007/5/23, Himanshu Khandelia <hkhandel_at_memphys.sdu.dk>:
>> >>>>>>
>> >>>>>>> Hello,
>> >>>>>>>
>> >>>>>>> Most NAMD papers describe a simulation timestep of 1 fs, no
>> >>>>>>> shake, a nonbondedfreq of 2, and an fullelecfreq. of 4. This
>> >>>>>>> is also what is recommended in most NAMD tutorials.
>> >>>>>>>
>> >>>>>>> However, use of a 2 fs timestep, a value of 1 for both the
>> >>>>>>> nonbondedfreq and fullelecfreq results in 15-25 % faster
>> >>>>>>> performance in my tests. I can provide more details of the
>> >>>>>>> tests if desired, but surely these tests must
>> >>>>>>> have already been performed.
>> >>>>>>>
>> >>>>>>> So why is SHAKE/RATTLE and a larger time step not being used
>> >>>>>>> for most simulations?
>> >>>>>>>
>> >>>>>>> Thank you for the help,
>> >>>>>>>
>> >>>>>>> -Himanshu
>> >>>>>>>
>> >>>>>>> ----------------------------
>> >>>>>>> Himanshu Khandelia, PhD
>> >>>>>>> Research Assistant Professor (Postdoc)
>> >>>>>>> MEMPHYS, Center for Membrane Physics: www.memphys.sdu.dk
>> >>>>>>> University of Southern Denmark (SDU) Odense M 5230, Denmark
>> >>>>>>>
>> >>>>>>> Phone: +4565503510
>> >>>>>>> email: hkhandel_at_memphys.sdu.dk
>> >>>>>>> WWW: www.memphys.sdu.dk/~hkhandel
>> >>>>>>> -----------------------------
>> >>>>>>>
>> >>>>>>>
>> >>>>>>>
>> >>>>>>>
>> >>>>> --
>> >>>>> 4330 Siebel Center
>> >>>>> 201 N. Goodwin Ave.
>> >>>>> Urbana, IL 61801
>> >>>>> http://www.cse.uiuc.edu/~ericcyr/
>> >>>>>
>> >>>>>
>> >>> -----------------------------------------------------
>> >>> 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.
>> >>> -----------------------------------------------------
>> >>>
>> >>>
>>

This archive was generated by hypermail 2.1.6 : Wed Feb 29 2012 - 15:44:45 CST