From: Jerome Henin (jhenin_at_cmm.chem.upenn.edu)
Date: Wed Nov 26 2008 - 10:16:12 CST
Peter: to answer your question about a frame being a "state", here
Steve is using the word in the sense of microstate.
Steve: since you are interested in statistics in conformation space,
if I were you I'd try reweighting based on the potential energy only
(using the target temperature as you did: I don't think the
instantaneous "temperature" is meaningful). You can always think of
your MD trajectories as if they were MC.
On Wed, Nov 26, 2008 at 1:18 AM, Steven Samuel Plotkin
> Hi Peter,
> Yes I am careful to get good equilibrium sampling by writing each "state" to
> the log and dcd files every 20ps. The reweighting of states should be
> independent of whatever reduced coordinate I choose, I think. However there
> are 2 ways to do the reweighting, and I'm not sure which is the appropriate
> one. One is to use T_real for the current temperature of the state, the
> other is to use T_targ for the current temperature of the state. I noticed
> that the state that dominated my statistics had an anomalously high T_real.
> Here is a segment of the Temperatures T_real (blue) and T_targ (green) vs
> The blue peak in the graph corresponds to the state that dominated my
> statistics. I think the reweighting is best done with T_targ rather than
> T_real, which gives a more robust answer. Does that make sense? The T_real's
> fluctuate about the target temperatures. ( I have to apologize for my
> confusing notation previously, where I used T_target for the temperature I
> want to obtain my free energy surface at. )
> Using T_targ instead of T_real alleviated but did not eliminate the problem.
> I think I simply need to collect more statistics. I thought 8000 states
> would be enough for a decent 1-dimensional free energy surface but
> apparently not in this case (the free E vs RMSD is quite rugged).
> The NVT simulations seem to be running fine.
> Thanks for your latest advice-- I do realize this thread has lately had more
> to do with data analysis than with the workings of NAMD.
> Peter Freddolino wrote:
> Hi Steve,
> I'm a little unclear on what you're doing... are you labeling as a "state"
> each single frame from your trajectory? This is unlikely to give good
> statistics as you need to average over solvent conformations and such (not
> to mention local fluctuations in the protein). Or are you defining some set
> of reduced coordinates to calculate your free energy surface? In the latter
> case I'd recommend looking over some papers in the literature with complete
> solutions for applying WHAM-style analysis to replica exchange simulations:
> J. Phys. Chem. B, 2005, 109 (14), pp 6722–6731
> JCTC, 2007, 3, pp 26-41
> All you should need to do to run at constant volume is turn off
> langevinPiston and comment out the settings following it.
> Steven Samuel Plotkin wrote:
> Hi Peter,
> I think you are right, and this was why I took the total energies initially,
> which includes both KE and PE of the whole peptide plus water. This is what
> governs the original sampling probabilities, so I have discarded the idea of
> cherry-picking parts of the system. To find the re-weighted probabilities
> for each state I have been simply reweighting each state by the factor:
> exp( E_i ( beta_i - beta_targ) )
> where E_i is the total energy of the state, beta_i is 1 over kB times the
> temperature at that sample time, and beta_targ is 1 over kB times the target
> temperature. This should be fine I think, at least for const volume
> After doing this re-weighting however, the new exponents in the Boltzmann
> factors are (when sorted from highest)
> so one particular state ends up having all the Boltzmann weight in the
> partition function (i.e. exp(16.3) more weight than the next weightiest
> state). I didn't think this was reasonable, it says entropy isnt important
> in the partition function. What are the solutions for this problem? Perhaps
> more sampled configurations, but I have 8000 now which I thought should be
> enough to at least get a rough idea what the potential looks like. Maybe I
> need a narrower temperature range- the beta_i - beta_targ factors are making
> the exponents too large. However previous studies of REMD seem to have gone
> to 500K without difficulty... I must be missing something.
> I did not add a pressure correction to the replica exchange scripts. I
> hadn't thought this through carefully enough and didn't know the REMD
> scripts had not accounted for it. According to the reference you mentioned,
> there is an extra term in the transition matrix, and an extra term in the
> probabilities ~ Vi^N exp(-beta P V_i ). I will have to check how large this
> factor is. I don't think the volume fluctuations should be very large but I
> could be wrong. Then I would have to rerun my simulations at constant
> volume. I assume from reading some previous posts on the forum that removing
> all statements pertaining to pressure and variable volume such as
> useGroupPressure yes ;# needed for rigidBonds
> useFlexibleCell no
> useConstantArea no
> langevinPiston on
> langevinPistonTarget 1.01325 ;# in bar -> 1 atm
> langevinPistonPeriod 100.
> langevinPistonDecay 50.
> from the conf file should do the trick.
> Thanks for any help,
> Peter Freddolino wrote:
> By the way, regarding the text below... I do not think that you should be
> taking the energies of a subset of your system to use in the analysis. You
> really ought to be using the total energy of your system for doing the type
> of analysis that you're doing; otherwise you're basically cherry-picking
> part of the total energy of your system without regard for the system as a
> whole. There are several variants of WHAM for analyzing replica exchange
> data in the literature that should be applicable to your problem. Also, the
> namd replica exchange scripts don't contain a pressure correction (Chem.
> Phys. Lett. 335:435–439.), so you should be running each simulation at
> constant volume unless you've added it...
> Steven Samuel Plotkin wrote:
> Dear NAMD users,
> I have run namdEnergy on a dcd file, printing out All energies. First I
> noticed the kinetic energy was not printed, then I compared the "TOTAL"
> potential energy from namdEnergy with the TOTAL energy minus the KINETIC
> energy in my log file. The two are quite different -- about 370 kcal/mol on
> average. I'm confused by this, I'm not sure what is being calculated
> differently? I've provided links to my dcd, log, namdEnergy settings, and
> conf file are below. I've also posted a long version of my question below to
> help put it in context.
> (I'm using namd 2.6 and vmd 1.8.6).
> Thanks for any help,
> Steve P.
> log and dcd file:
> Conf files:
> Screenshot of my namdEnergy gui, with settings:
> xsc file (if needed):
> /Long version of my question:/
> I have been able to modify the Alanin replica exchange tcl code to run on a
> small peptide which has been solvated and is in ionic solution. I am using
> namd 2.6 on an x86_64 amd cluster. I ran 16 replicas on 8 CPUs across 2
> nodes of a cluster, with temperatures ranging from 280K to 440K. My conf
> file has some new information not in the alanin example because of my
> solvated box: I have cellBasisVectors, wrapWater, wrapAll, PME, and Pressure
> control options including langevinPiston. I was careful to choose the
> langevinPistonTemp to be $NEWTEMP in replica_exchange.tcl.
> I want to construct a free energy profile for the small peptide. However
> this must be obtained at one (target) temperature, so I reweighted all
> states by what their Boltzmann weights should have been at the target
> temperature. This doesn't work for me: because the system includes the
> peptide plus the whole water box, after re-weighting, one particular state
> ends up having all the Boltzmann weight in the partition function. I didn't
> think this was feasible.
> So then what I must use is the total energy (KE +PE) of the protein itself,
> which includes self interactions /plus/ interactions with water and ions.
> Then I can reweight these energies at the target temperature and get a new
> partition function and free energy profile. I thought namdEnergy would be
> the tool for this.
> As a sanity check, I ran namdEnergy on one of my dcd files, printing out
> 'All' energies. First I noticed the kinetic energy was not printed, then I
> compared the "TOTAL" potential energy with the TOTAL energy minus the
> KINETIC energy in my log file. The two are quite different -- about 370
> kcal/mol on average. However the average total potential energy is about
> 4460 kcal/mol, so the mean error is about 8%. Am I doing something wrong
> here? Or is this to be expected?
> At the end of the day what I believe I want is simply the namdEnergy numbers
> for selection 1= PROTEIN , selection 2= "everything else", added to the
> PROTEIN-PROTEIN namdEnergies. However the errors present in my sanity check
> are giving me pause that the namdEnergies are trustable.
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