SPAM throws error of 'std::bad_alloc'

[DDGmichigan]

I am using spam to calculate free energies for a mixed solvent MD simulation (protein is ABL kinase)
My input file is as follows:
parm /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_9pmemdcuda/3kfa_layer_ACN_H2O_5-95vv.prmtop
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_1-pmemdMPI/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_1-pmemdMPI/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_2pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_2pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_3pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_3pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_4pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_4pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_5pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_5pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_6pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_6pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_7pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_7pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_8pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_8pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_9pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_9pmemdcuda/New4H_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_10pmemdcuda/New4G_production.1.crd 1 50 1
trajin /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/3kfa_md_10pmemdcuda/New4H_production.1.crd 1 50 1

#Center and process image
##center :1-286 mass origin
##image origin familiar com :1-286

autoimage
##Align trajectory to reference structure by minimizing RMSD
reference /users/dicksmit/gphani/unsabi/users2/gphani/3_mixMD/ablkinase_3KFA/ACN_H2O_5-95vv_layered/setup_solvbox/3kfa_layer_ACN_H2O_5-95vv.pdb
strip :Cl-,Na+
rms reference mass out 3kfa_ACN_15-20ns_md_CA_rmsd.txt :1-286@CA
spam 3kfa_ACN_peak.xyz solv C3N reorder cut 12 sphere site_size 6 dgbulk -30.3 dhbulk -22.2 info info.txt summary spam_summary.out out spam_energies.out

Error I get is:

Read 1000 frames and processed 1000 frames.
TIME: Avg. throughput= 16.8114 frames / second.

ACTION OUTPUT:
SPAM timing data:
TIME: Residue c.o.m. calc: 0.0058 s ( 0.02%)
TIME: Peak assignment : 0.0196 s ( 0.07%)
TIME: Occupancy calc. : 0.0013 s ( 0.00%)
TIME: Energy calc : 27.4013 s ( 99.89%)
TIME: Residue reordering : 0.0040 s ( 0.01%)
TIME: SPAM Action Total: 27.4324 s
terminate called after throwing an instance of 'std::bad_alloc'
what(): std::bad_alloc
Aborted (core dumped)

[drroe]

I'll probably need files so I can reproduce the error. The topology and a few coordinate frames should suffice.

[DDGmichigan]

Sure Dan. I will send them to you asap. Thanks for replying

[DDGmichigan]

traj+prmtop.zip

[drroe]

Thanks for the files. However, I wasn't able to reproduce the segfault (using version 4.12.1). Could you send me the peaks file you are using as well? Also the input you used to generate the peaks file (in particular, I would like to see the exact volmap command you used). I'll paste the input I successfully used below.

Also, I noticed some issues with how you are currently doing your calculation. If you look at the output from the autoimage command you'll notice that your C3N residues are "fixed" to your anchor (which you probably do not want) because they are not considered solvent molecules by default. You should add the following before autoimage:

solvent :WAT,C3N

My volmap input:

parm 3kfa_layer_ACN_H2O_5-95vv.prmtop
trajin New4E_production.1.crd
solvent :C3N,WAT
autoimage
strip :Cl-,Na+
rms first mass out 3kfa_ACN_15-20ns_md_CA_rmsd.txt :1-286@CA
volmap :C3N centermask ^1 buffer 5.0 peakfile 3kfa_ACN_peak.xyz dx 1.0

My spam input:

parm 3kfa_layer_ACN_H2O_5-95vv.prmtop
trajin New4E_production.1.crd
solvent :WAT,C3N
autoimage
strip :Cl-,Na+
rms first mass out 3kfa_ACN_15-20ns_md_CA_rmsd.txt :1-286@CA
spam 3kfa_ACN_peak.xyz solv C3N reorder cut 12 sphere site_size 6 \
     dgbulk -30.3 dhbulk -22.2 info info.txt summary spam_summary.out \
     out spam_energies.out

[DDGmichigan]

Hi, Sounds weird as to why I am getting the error!
Attached is a peakfile input I used.
I have also attached a file MixMD_energies.pdb , it contains the x,y,z coordinates followed by net free energy of binding at that hotspot.
sample file looks like this
ATOM 1 XX UNX A 1 -6.000 14.000 -2.500 0.00 -1.880542
ATOM 1 XX UNX A 2 -4.500 16.000 -7.000 0.00 -1.864117
ATOM 1 XX UNX A 3 0.000 0.500 12.000 0.00 -1.668812
ATOM 1 XX UNX A 4 1.000 -3.500 9.500 0.00 -1.621935
ATOM 1 XX UNX A 5 4.000 23.000 -3.500 0.00 -1.465110
ATOM 1 XX UNX A 6 0.000 22.000 20.500 0.00 -1.435783

I have a small script which converts this file to peakfile.xyz.
When this failed, I got segfault errors, I used the volmap command to generate the peakfile
My vomap command is " volmap volmap_C3N.xplor 0.5 0.5 0.5 :C3N@C2 name GRID size 200,200,200 peakcut 0.001 peakfile 3kfa_ACN_peak.xyz"

Even then the error
files.zip
persisted

[drroe]

Even with your peaks file, I can't reproduce the segfault. I checked with valgrind and there are no memory shenanigans going on. Can you post the output of cpptraj --internal-version?

Can you try running with the input I provided (both for generating the peaks with volmap and the spam command) and see if you still get the segfault?

[DDGmichigan]

[3kfa_ACN_xplor_bind_energ_last5ns_10runs]$ cpptraj --version
CPPTRAJ: Version V4.12.2 (GitHub)
Its my bad luck that the error is not popping up today, maybe it was a bad day yesterday when I tried, let me try it once more and then shall get back to you. I did not mean to waste your valuable time over this. I am sorry!

[drroe]

No worries - code should never segfault so I'd like to get to the bottom of it. If you can still reproduce the segfault I may have you run valgrind to do a more in-depth memory check if you don't mind.

[DDGmichigan]

Absolutely! I am sitting with it today afternoon and shall get back to you with updates! Thanks for being so helpful Regards Debarati Sent from Mail<https://go.microsoft.com/fwlink/?LinkId=550986> for Windows 10

…

________________________________ From: Daniel R. Roe <notifications@github.com> Sent: Thursday, May 2, 2019 10:22:49 AM To: Amber-MD/cpptraj Cc: DDGmichigan; Author Subject: Re: [Amber-MD/cpptraj] SPAM throws error of 'std::bad_alloc' (#710) No worries - code should never segfault so I'd like to get to the bottom of it. If you can still reproduce the segfault I may have you run valgrind to do a more in-depth memory check if you don't mind. — You are receiving this because you authored the thread. Reply to this email directly, view it on GitHub<#710 (comment)>, or mute the thread<https://github.com/notifications/unsubscribe-auth/ALP3CAL66CSCPOXH7NUIZX3PTL2LTANCNFSM4HI2GIIQ>.

[DDGmichigan]

Hi Daniel,
There is no segfault issues now with SPAM but I have some scientific queries.

When I look at hotspots and evaluate the free energies of binding of ACN molecules on those hotspots I get negative energies of binding!
When I used the SPAM command to calculate the interaction energies, I get positive dG values which cannot be possible ideally, any clues as to what might be going on with the SPAM calculations.
It would immensely help
This is the output file named "SPAM_Summary.out"
#Peak SPAM_00001[DG] SPAM_00001[DH] SPAM_00001[-TDS]
1.000 3.8280 3.3674 0.4606
5.000 3.8842 2.6350 1.2492
7.000 4.0662 3.2994 0.7668
11.000 2.0295 3.1875 -1.1581
14.000 1.8901 3.6465 -1.7564
15.000 5.3431 3.2239 2.1192
16.000 -0.2742 3.2231 -3.4974
20.000 4.5459 3.1734 1.3726
21.000 1.0247 3.2657 -2.2410
25.000 4.0410 3.0492 0.9917
~

[DDGmichigan]

Also in the solvent command you added solvent :WAT,C3N

But I want to calculate the interaction energies of C3N molecules so why do I have to include WAT as my solvent?

[DDGmichigan]

Also, now in certain cases, I get this

ACTION OUTPUT:
SPAM timing data:
TIME: Residue c.o.m. calc: 0.2755 s ( 88.85%)
TIME: Peak assignment : 0.0011 s ( 0.37%)
TIME: Occupancy calc. : 0.0212 s ( 6.83%)
TIME: Energy calc : 0.0012 s ( 0.40%)
TIME: Residue reordering : 0.0012 s ( 0.39%)
TIME: SPAM Action Total: 0.3100 s
TIME: Analyses took 0.0000 seconds.

DATASETS (5 total):
GRID "GRID" (float grid), size is 64000000 (256.000 MB)
GRID[totalvol] "GRID[totalvol]" (double), size is 1 (0.008 kB)
SPAM_00003[DG] "SPAM_00003[DG]" (X-Y mesh), size is 0
SPAM_00003[DH] "SPAM_00003[DH]" (X-Y mesh), size is 0
SPAM_00003[-TDS] "SPAM_00003[-TDS]" (X-Y mesh), size is 0
Total data set memory usage is at least 256.000 MB

DATAFILES (5 total):
volmap_C3N.xplor (Xplor File): GRID
spam_energies.out (Standard Data File):
spam_summary.out (Standard Data File): SPAM_00003[DG] SPAM_00003[DH] SPAM_00003[-TDS]
3kfa_ACN_peak.xyz (Volmap Peaks)
info.txt (SPAM info)
Warning: File 'spam_energies.out' has no sets containing data.
Warning: Set 'SPAM_00003[DG]' contains no data.
Warning: Set 'SPAM_00003[DH]' contains no data.
Warning: Set 'SPAM_00003[-TDS]' contains no data.
Warning: File 'spam_summary.out' has no sets containing data.

RUN TIMING:
TIME: Init : 0.0140 s ( 0.01%)
TIME: Trajectory Process : 126.1016 s ( 99.99%)
TIME: Action Post : 0.0002 s ( 0.00%)
TIME: Analysis : 0.0000 s ( 0.00%)
TIME: Data File Write : 0.0003 s ( 0.00%)
TIME: Other : 0.0001 s ( 0.00%)
TIME: Run Total 126.1161 s
---------- RUN END ---------------------------------------------------
TIME: Total execution time: 2491.8533 seconds.

To cite CPPTRAJ use:
Daniel R. Roe and Thomas E. Cheatham, III, "PTRAJ and CPPTRAJ: Software for
Processing and Analysis of Molecular Dynamics Trajectory Data". J. Chem.
Theory Comput., 2013, 9 (7), pp 3084-3095.

There is no data inside peakfile output and no output in spam_energies.out
Any reason for this?

[drroe]

Without seeing the files it's hard to tell. It could be that the coordinates you used when you calculated your peaks (i.e. any centering/rotating/etc that you did) isn't corresponding to the coordinates you're using when running SPAM (i.e. you're not centering/rotating them the same way), so the peaks don't actually correspond to what SPAM expects. Again, I'd need some files to reproduce before I could say for certain.

[DDGmichigan]

Hi Daniel, I can send you the input files and relevant stuff so that you can reproduce the error. The issue I am facing has to do with the values. After having located the hotspots I have used the same x,y,z coordinates in my spam peakfile and the free energies I get is positive for the exact spot where MixMD, SILCS etc methods gave a negative value, even LIE. So I am confused as to what different things may be happening that I do not get favorable energies using SPAM analysis.

[DDGmichigan]

input.zip