Feature #742
Enhancing the performance of the free energy code
Description
Dear all,
free energy perturbation (FEP) module of GROMACS 4.5 can be used to perform
Hamiltonian replica exchange molecular dynamics (H-REMD). The main modules that "drive"
H-REMD simulation are src/kernel/repl_ex.c and /src/gmxlib/nonbonded/ nb_free_energy.c
I tried to perform H-REMD decoupling a small peptide in
water. In this case I observed about a 40-50% reduction in speed.
When I tried to decouple water and peptide the performance loss is much more dramatic.
I posted my test files in:
https://www.dropbox.com/link/17.-sUcJyMeEL?k=0f3b6fa098389405e7e15c886dcc83c1
This is a run for a dialanine peptide in a water box.
The cell side cubic box was 40 A.
The directory is organized as :
TEST\
topol.top
Run-00/confout.gro ; Equilibrated structure
Run-00/state.cp
MD-std/Commands ; commands to run the simulation , grompp and mdrun
MD-std/md.mdp
MD-FEP/Commands
MD-FEP/md.mdp
For more details in this issue see also gmx-users mailing list:
http://lists.gromacs.org/pipermail/gmx-users/2011-April/060169.html
FEP code is bug free, but a this stage it is unusable to perform H-REMD
due to the low performance.
Free Energy Perturbation with Replica Exchange Molecular Dynamics offers
a powerful strategy to enhance the sampling of biological system, therefore
I would suggest to improve its efficiency.
Best regards
Luca
Subtasks
Related issues
History
#1 Updated by Rossen Apostolov almost 6 years ago
- Project changed from 9 to GROMACS
#2 Updated by Chris Neale over 3 years ago
I would like to add some more information to show how slow this can be. It's basically not an option and yet one wonders why hamiltonian replica exchange should be so slow. My guess is that the code is now computing a whole bunch of things that might be useful for mbar If this is the case, it would be great if there were an option to turn all of that part off since the extra efficiency of mbar vs. wham is unlikely to overcome a 10x performance loss during sampling. I provide information below, in which I am using H-REMD to partially decouple lipids in a bilayer, which enhances relaxation times ( http://pubs.acs.org/doi/pdf/10.1021/ct500305u -- though these authors rewrote the HREX code to avoid the really slow speed they also got when decoupling lots of atoms ).
Below is information from either (a) temperature REMD (T-REMD) in gromacs 5.1.2 or (b) Hamiltonian REMD (H-REMD), also in gromacs 5.1.2.
Here is the .mdp for my lowest temperature in T-REMD:
$ cat REMD/MD_0.mdp nsteps = 500000000 integrator = sd dt = 0.002 tinit = 0 lincs-iter = 1 lincs-order = 6 constraint_algorithm = lincs ;;; charmm section from http://www.gromacs.org/Documentation/Terminology/Force_Fields/CHARMM constraints = h-bonds cutoff-scheme = Verlet vdwtype = cutoff vdw-modifier = force-switch rlist = 1.2 rvdw = 1.2 rvdw-switch = 1.0 coulombtype = PME rcoulomb = 1.2 DispCorr = no ns_type = grid nstcomm = 100 nstxout = 0 nstvout = 0 nstfout = 0 nstxtcout = 50000 nstenergy = 50000 nstlist = 10 nstlog=0 ; reduce log file size ewald-rtol = 1e-5 fourierspacing = 0.12 fourier_nx = 0 fourier_ny = 0 fourier_nz = 0 pme_order = 4 tc_grps = System tau_t = 1.0 ld_seed = -1 ref_t = 310 gen_temp = 310 gen_vel = yes unconstrained_start = no gen_seed = -1 Pcoupl = berendsen pcoupltype = isotropic tau_p = 4 compressibility = 4.5e-5 ref_p = 1.0
And here is a diff of the the above .mdp file with the first replica's mdp file in H-REMD:
$ diff REMD/MD_0.mdp REST/MD_0.mdp 54a55,67 > free_energy = yes > couple-lambda0 = vdw-q > couple-lambda1 = none > init_lambda_state = 0 > couple-moltype = POPC > couple-intramol = yes > nstdhdl = 200 > vdw_lambdas = 0 0.01 0.02 0.03 > coul_lambdas = 0 0.01 0.02 0.03 > bonded_lambdas = 0 0.01 0.02 0.03 > calc-lambda-neighbors = 1 > dhdl-derivatives = no
Here is the time accounting in T-REMD:
M E G A - F L O P S A C C O U N T I N G
NB=Group-cutoff nonbonded kernels NxN=N-by-N cluster Verlet kernels
RF=Reaction-Field VdW=Van der Waals QSTab=quadratic-spline table
W3=SPC/TIP3p W4=TIP4p (single or pairs)
V&F=Potential and force V=Potential only F=Force only
Computing: M-Number M-Flops % Flops
-----------------------------------------------------------------------------
NB VdW [V&F] 659.164520 659.165 0.0
Pair Search distance check 14222.443774 128001.994 0.3
NxN Ewald Elec. + LJ [F] 487803.315024 38048658.572 93.0
NxN Ewald Elec. + LJ [V&F] 4939.855840 637241.403 1.6
NxN Ewald Elec. [F] 1724.128368 105171.830 0.3
NxN Ewald Elec. [V&F] 17.509568 1470.804 0.0
1,4 nonbonded interactions 959.220040 86329.804 0.2
Calc Weights 1857.790560 66880.460 0.2
Spread Q Bspline 39632.865280 79265.731 0.2
Gather F Bspline 39632.865280 237797.192 0.6
3D-FFT 136008.942660 1088071.541 2.7
Solve PME 63.841600 4085.862 0.0
Reset In Box 25.794240 77.383 0.0
CG-CoM 26.818560 80.456 0.0
Bonds 130.875280 7721.642 0.0
Propers 1120.420080 256576.198 0.6
Impropers 3.192080 663.953 0.0
Virial 63.017890 1134.322 0.0
Update 619.263520 19197.169 0.0
Stop-CM 6.223520 62.235 0.0
P-Coupling 61.924800 371.549 0.0
Calc-Ekin 248.739040 6715.954 0.0
Lincs 470.676246 28240.575 0.1
Lincs-Mat 4341.725248 17366.901 0.0
Constraint-V 1582.080664 12656.645 0.0
Constraint-Vir 55.582336 1333.976 0.0
Settle 213.582628 68987.189 0.2
-----------------------------------------------------------------------------
Total 40904820.504 100.0
-----------------------------------------------------------------------------
D O M A I N D E C O M P O S I T I O N S T A T I S T I C S
av. #atoms communicated per step for force: 2 x 25405.3
av. #atoms communicated per step for LINCS: 2 x 1980.1
Average load imbalance: 0.8 %
Part of the total run time spent waiting due to load imbalance: 0.6 %
Steps where the load balancing was limited by -rdd, -rcon and/or -dds: X 0 %
R E A L C Y C L E A N D T I M E A C C O U N T I N G
On 6 MPI ranks
Computing: Num Num Call Wall time Giga-Cycles
Ranks Threads Count (s) total sum %
-----------------------------------------------------------------------------
Domain decomp. 6 1 1727 3.731 55.836 1.0
DD comm. load 6 1 1661 0.005 0.068 0.0
DD comm. bounds 6 1 1727 0.029 0.434 0.0
Neighbor search 6 1 1662 6.904 103.323 1.9
Comm. coord. 6 1 38239 1.930 28.878 0.5
Force 6 1 39901 277.306 4149.961 76.4
Wait + Comm. F 6 1 39901 1.729 25.870 0.5
PME mesh 6 1 39901 40.715 609.316 11.2
NB X/F buffer ops. 6 1 116379 1.624 24.304 0.4
Write traj. 6 1 2 1.016 15.209 0.3
Update 6 1 79802 5.591 83.675 1.5
Constraints 6 1 79802 17.926 268.266 4.9
Comm. energies 6 1 8046 1.191 17.831 0.3
Rest 3.058 45.769 0.8
-----------------------------------------------------------------------------
Total 362.756 5428.739 100.0
-----------------------------------------------------------------------------
Breakdown of PME mesh computation
-----------------------------------------------------------------------------
PME redist. X/F 6 1 79802 4.783 71.572 1.3
PME spread/gather 6 1 79802 19.101 285.848 5.3
PME 3D-FFT 6 1 79802 9.627 144.068 2.7
PME 3D-FFT Comm. 6 1 79802 5.029 75.263 1.4
PME solve Elec 6 1 39901 2.096 31.374 0.6
-----------------------------------------------------------------------------
Core t (s) Wall t (s) (%)
Time: 2165.027 362.756 596.8
(ns/day) (hour/ns)
Performance: 19.007 1.263
Finished mdrun on rank 0 Mon Mar 28 21:02:03 2016
Here is the time accounting in H-REMD:
M E G A - F L O P S A C C O U N T I N G
NB=Group-cutoff nonbonded kernels NxN=N-by-N cluster Verlet kernels
RF=Reaction-Field VdW=Van der Waals QSTab=quadratic-spline table
W3=SPC/TIP3p W4=TIP4p (single or pairs)
V&F=Potential and force V=Potential only F=Force only
Computing: M-Number M-Flops % Flops
-----------------------------------------------------------------------------
NB VdW [V&F] 57.423520 57.424 0.0
NB Free energy kernel 3335062.688538 3335062.689 47.4
Pair Search distance check 1239.899470 11159.095 0.2
NxN Ewald Elec. + LJ [F] 42585.090944 3321637.094 47.2
NxN Ewald Elec. + LJ [V&F] 445.850656 57514.735 0.8
NxN Ewald Elec. [F] 147.593376 9003.196 0.1
NxN Ewald Elec. [V&F] 1.507392 126.621 0.0
1,4 nonbonded interactions 83.563040 7520.674 0.1
Calc Weights 161.842560 5826.332 0.1
Spread Q Bspline 6905.282560 13810.565 0.2
Gather F Bspline 6905.282560 41431.695 0.6
3D-FFT 23697.004320 189576.035 2.7
Solve PME 11.123200 711.885 0.0
Reset In Box 2.250400 6.751 0.0
CG-CoM 2.343520 7.031 0.0
Bonds 11.401280 672.676 0.0
Propers 97.606080 22351.792 0.3
Impropers 0.278080 57.841 0.0
Virial 5.510710 99.193 0.0
Update 53.947520 1672.373 0.0
Stop-CM 0.558720 5.587 0.0
P-Coupling 5.400960 32.406 0.0
Calc-Ekin 21.681440 585.399 0.0
Lincs 41.048794 2462.928 0.0
Lincs-Mat 377.249760 1508.999 0.0
Constraint-V 137.970858 1103.767 0.0
Constraint-Vir 4.865245 116.766 0.0
Settle 18.630994 6017.811 0.1
-----------------------------------------------------------------------------
Total 7030139.356 100.0
-----------------------------------------------------------------------------
D O M A I N D E C O M P O S I T I O N S T A T I S T I C S
av. #atoms communicated per step for force: 2 x 25389.0
av. #atoms communicated per step for LINCS: 2 x 2001.2
Average load imbalance: 1.4 %
Part of the total run time spent waiting due to load imbalance: 1.3 %
Steps where the load balancing was limited by -rdd, -rcon and/or -dds: X 0 %
R E A L C Y C L E A N D T I M E A C C O U N T I N G
On 6 MPI ranks
Computing: Num Num Call Wall time Giga-Cycles
Ranks Threads Count (s) total sum %
-----------------------------------------------------------------------------
Domain decomp. 6 1 150 0.328 4.904 0.1
DD comm. load 6 1 144 0.001 0.008 0.0
DD comm. bounds 6 1 150 0.003 0.049 0.0
Neighbor search 6 1 145 1.961 29.340 0.5
Comm. coord. 6 1 3331 0.185 2.772 0.1
Force 6 1 3476 342.581 5126.810 93.3
Wait + Comm. F 6 1 3476 0.158 2.361 0.0
PME mesh 6 1 3476 10.697 160.076 2.9
NB X/F buffer ops. 6 1 10138 0.154 2.302 0.0
Write traj. 6 1 2 1.142 17.092 0.3
Update 6 1 6952 0.497 7.431 0.1
Constraints 6 1 6952 5.805 86.867 1.6
Comm. energies 6 1 701 1.161 17.371 0.3
Rest 2.342 35.055 0.6
-----------------------------------------------------------------------------
Total 367.012 5492.439 100.0
-----------------------------------------------------------------------------
Breakdown of PME mesh computation
-----------------------------------------------------------------------------
PME redist. X/F 6 1 10428 5.509 82.446 1.5
PME spread/gather 6 1 13904 2.333 34.909 0.6
PME 3D-FFT 6 1 13904 1.655 24.762 0.5
PME 3D-FFT Comm. 6 1 13904 0.835 12.500 0.2
PME solve Elec 6 1 6952 0.352 5.264 0.1
-----------------------------------------------------------------------------
Core t (s) Wall t (s) (%)
Time: 2196.030 367.012 598.4
(ns/day) (hour/ns)
Performance: 1.637 14.665
Finished mdrun on rank 0 Mon Mar 28 22:31:05 2016
Both were run like this:
ibrun -np 24 /oasis/scratch/comet/cneale/temp_project/exec/gromacs-5.1.2/exec_openmpi/bin/gmx_mpi mdrun -notunepme -deffnm MD_ -dlb yes -npme 0 -cpt 60 -maxh 0.1 -cpi MD_.cpt -multi 4 -replex 200
There is the plumed route, which is viable and I have used it. The problem is that the plumed release cycle lags behind the gromacs release cycle and so some of the efficiencies and options in newer gromacs versions are not always available when using plumed to do the coupling.
Thank you,
Chris.
#3 Updated by Mark Abraham over 3 years ago
- Target version set to future
As noted in discussion on gmx-users, the performance of the GROMACS free-energy kernels is indeed relatively poor. It seems likely we can do a lot better, once we have some new infrastructure sorted out. But that won't happen before GROMACS 2017, sorry.
#4 Updated by Chris Neale over 3 years ago
- File RESTandREMDtprs.tgz RESTandREMDtprs.tgz added
tarball uploaded with .tpr and short run outputs for a single system with both T-REMD and H-REMD (the later to do REST). README file describing usage is enclosed. Please note the system is quite small because it is designed for testing only. I realize that the problem here is that I'm trying to use a tool outside of its design specifications and that the free energy code has a lot of parts that are really useful for decoupling a small number of atoms. However, one would hope that eventually we can somehow decouple large numbers of atoms without taking more than a 5% efficiency hit if we are willing to give up some of the useful PMF-related tools available in the core free energy code. Of course, there would have to be sufficient interest and that part is not clear.
#5 Updated by Mark Abraham over 3 years ago
- Related to Feature #1665: improve free energy non-bonded kernel performance added
#6 Updated by Mark Abraham over 3 years ago
- Target version changed from future to 2018
Noted. Chris's reported slowdown (factor of ~13 in number of steps in that -maxh, attributable to the branchy FE code path and lack of SIMD support, in his case) is indeed horrible. There is a rather extreme amount of configurability in the free-energy kernel, but one of the planned advantages of the new kernel generation scheme is that we can probably support a mode where by default one gets a slow kernel like now, but perhaps issues a run-time warning about how one can do a custom CMake call to optimize for the actual target(s) required in a future run. Or maybe (simpler) a "really, I don't care, compile everything" configuration option.
It's possible to make a start on that even before the new scheme materializes - compiling out run-time constants can take place even if the kernels are still using group-scheme neighbourlists and no SIMD. Or maybe it's easier to start from a modified form of the Verlet plain C kernels?
My suspicion is that Chris's "extra stuff for mbar" theory isn't the main problem, but I'd verify that before starting work.
#7 Updated by Mark Abraham about 3 years ago
- Related to Bug #2014: GROMACS free energy memory footprint added
#8 Updated by Mark Abraham over 2 years ago
- Target version changed from 2018 to future
I'm not aware of work underway that could be done in time for 2017 release
#9 Updated by Sebastian Wingbermühle almost 2 years ago
- File standardMD.tpr standardMD.tpr added
- File FEP.tpr FEP.tpr added
- File nb_free_energy.cpp nb_free_energy.cpp added
- File standardMD.log standardMD.log added
- File FEP.log FEP.log added
- File tuned-FEP.log tuned-FEP.log added
Hello!
Here are some results concerning the performance of the FEP code compared to standard MD simulations using alanine dipeptide in TIP4P water as test system (see .tpr files attached). The simulations were intended to be a performance test for the solute tempering approach known from replica exchange. Therefore, the potential energy terms of the complete alanine dipeptide are scaled, whereas the potential energy of the water is not modified. In this setup, lambda = 0 corresponds to the state in which the potential of alanine dipeptide is not changed and lambda = 1 means full scaling. For a fair comparison, physically identical simulations were carried out, i.e. standard MD simulations are compared to simulations using the FEP code with lambda = 0. Soft-core potentials and BAR/MBAR calculations were turned off. Moreover, I modified the non-bonded free-energy kernel by commenting out all if-loops and switch-case constructions dealing with different user options for the treatment of Coulomb and van der Waals interactions such that the resulting kernel can only be used for my settings (see attached). The performance obtained with the modified kernel is listed as "tuned FEP" below. Further technical details are:
version:
GROMACS 2016.3
command to launch simulations:
gmx mdrun -pin on -deffnm REST -cpnum -cpt 60 -cpo cpt/state
hardware:
CPU: Xeon E3-1270 V2 CPUs (4 cores at 3.5 GHz)
GPU: 1 Nvidia GeForce GTX 770 graphics card (1536 CUDA cores at 1.0 GHz and 2 GB GDDR5 (non-ECC) memory)
Results (compare .log files attached for further details):
Setup Performance (ns/day)
standard MD 490.878
FEP 126.319
tuned FEP 132.393
#10 Updated by Mark Abraham over 1 year ago
Thanks for the feedback. We know these kernels are a problem that needs quite a bit of attention. One useful tip is that the intel compiler does a much better job than gcc on the FEP short-range interactions that are the bulk of the problem here. Your data is interesting because it seems to suggest that the performance improvement from icc is probably more about better vectorization than better code generation in the face of lots of branches.
#11 Updated by Roland Schulz over 1 year ago
Could you update the tpr files or upload the files to generate the tpr files? Those tpr can't be execute with 2018 version.
#12 Updated by Mark Abraham about 1 year ago
- Related to Feature #2601: Free energy calculations, soft-core potential added
#13 Updated by Magnus Lundborg about 2 months ago
- File testosterone_lj_decoupling.tpr testosterone_lj_decoupling.tpr added
- File testosterone_q_decoupling.tpr testosterone_q_decoupling.tpr added
Two more examples of affected systems attached.
#14 Updated by Magnus Lundborg about 2 months ago
This is the same system as above, but without FE.
#15 Updated by Berk Hess about 2 months ago
I would suggest an approach analogous to do_pairs_simple()
We should vectorize over j and duplicate the last j to get to multiples of the SIMD width. Then nearly all reals in the kernel needs to be templated, so they can be real or a simd real.
For good performance we likely need to template the kernel on interaction types to get rid of all conditionals.
All off this should be rather straightforward, I think.