VMD-L Mailing List

From: Mayne, Christopher G (cmayne2_at_illinois.edu)
Date: Mon Jul 24 2017 - 22:28:54 CDT

Scott,

One thing to note that is potentially a problem are the interactions which end at +/-0.4 Å. By default ffTK only scans distances +/- 0.4 Å from the QM-optimized distance; so, when waters end at that distance, it is most likely not an actual position of minimum MM energy, but rather just the end of the allowed range. This can be adjusted by changing the MM shift range in the Advanced Settings section. If the MM optimization is pushing the water further than that, then something else is quite wrong.

Perhaps more important, however, is that getting the energies of the interaction to match up is much more important the distances. I typically weight the energies at least 2:1 over the distances.

I’m starting to settle in a new location, so if you continue to wrestle with this, send me the PSF, PDB and any relevant PAR files and the LOG files and I’ll take a look.

Regards,
Christopher Mayne

> On Jul 22, 2017, at 1:36 PM, McCullough, Scott <Scott.McCullough_at_indwes.edu> wrote:
>
>
> We are working on the charge optimization step for the parameterization of a SHP-2 inhibitor molecule. We are unable to get the QM/MM distances to align. The optimized charges converge and the objective function reaches a minimum. The QM/MM energy alignments are sort of ok (not as good as it should be), but the distances are awful. A “tail” of our last ChargeOpt.log file is shown below.
>
> One complication of the molecule is that a chlorine and 2 hydrogens form a tight triangle in the geometry optimized molecule. (We checked it more than once). This affects the
>
> We have tried a number of remedies.
>
> 0. We fixed the charges for atoms whose penalties from Paramchem were zero. These were typically ring carbons (and their hydrogens) not near heteroatoms. (This is standard practice, we think, rather than a remedy.)
> 1. We excluded QM water interaction files (Gaussian log files) for which there were errors or for which the optimal distance was too far away (several angstroms).
> 2. We likewise excluded QM water interactions for donor interactions if the charge and the acceptor interaction showed it was clearly an acceptor. (And vice versa.)
> 3. We refined QM water setup files (Gaussian input files) for a number of atoms.
> a. In the geometry-optimized configuration, 3 atoms (two hydrogens and a chlorine) form a triangle, and the usual choice of moving the water “straight away” from the ring resulted in high energy clashes with the neighbors. We reoriented the water molecules to move in a different direction that seemed to represent the most rapid departure from all other atoms. These QM files resulted in realistic equilibrium distances with the types (donor or acceptor) aligning with our intuition.
> b. One or two other atoms, one notably an oxygen, needed a different direction for the QM single-point energy calculations. Similar noises about distances and atom types.
> 4. In the charge optimization, we increased the weight for the distance to 3. Some distance differences (as seen in either the COLP or the log files) are zero, but many are still large – as much as 0.4 A (or more?).
> 5. We lastly tried excluded QM water interaction files for atoms whose charge was fixed (from CGenFF).
>
> We are at a loss as to what to try next. Grateful for any guidance.
>
> I can send pdb/psf, geometry opt files, etc if they would help.
>
> We are new to this work, but have read the CGenFF paper, the fftk paper and worked the tutorials and followed the workflow. I suspect we are doing something that someone with experience would say, “We never do that”, or not doing something that others would say, “We always do that.”
>
> With thanks,
>
> Scott
>
>
>
> Current test charges: C 0.085 N -0.264 C2 0.238 N2 -0.253 C3 0.239 H 0.171 O -0.429 C4 -0.074 H2 0.315 C5 -0.039 C6 -0.148 H3 0.350 C7 0.081 O2 -0.392 C10 0.266 O3 -0.368 C14 -0.135 H11 0.157 C15 0.139 CL -0.124 C16 -0.123 H12 0.127
> Iteration: 1937
> C3 QME: -0.761 MME: -1.826 (-1.065) QMD: 4.187 MMDistDelta: -0.400
> C4 QME: -1.787 MME: -2.786 (-0.999) QMD: 3.626 MMDistDelta: -0.200
> C5 QME: -1.538 MME: -1.502 (0.036) QMD: 3.772 MMDistDelta: -0.100
> C7 QME: -1.353 MME: -1.504 (-0.151) QMD: 3.791 MMDistDelta: -0.250
> C9 QME: -1.946 MME: -2.114 (-0.168) QMD: 3.664 MMDistDelta: -0.150
> C10 QME: -0.451 MME: -1.195 (-0.744) QMD: 4.439 MMDistDelta: -0.200
> C14 QME: -1.692 MME: -1.452 (0.240) QMD: 3.793 MMDistDelta: -0.250
> C15 QME: -2.690 MME: -3.591 (-0.901) QMD: 3.791 MMDistDelta: -0.300
> C16 QME: -3.206 MME: -3.997 (-0.791) QMD: 3.674 MMDistDelta: -0.300
> CL QME: -1.962 MME: -2.312 (-0.350) QMD: 3.782 MMDistDelta: -0.300
> N QME: -1.642 MME: -1.764 (-0.123) QMD: 3.340 MMDistDelta: 0.100
> N2 QME: -0.153 MME: -0.844 (-0.691) QMD: 4.337 MMDistDelta: -0.400
> O QME: -7.443 MME: -7.163 (0.280) QMD: 2.954 MMDistDelta: -0.050
> O QME: -6.942 MME: -6.667 (0.275) QMD: 2.956 MMDistDelta: -0.050
> O QME: -5.209 MME: -5.482 (-0.274) QMD: 3.039 MMDistDelta: -0.100
> O2 QME: -3.544 MME: -4.525 (-0.981) QMD: 3.234 MMDistDelta: -0.150
> O2 QME: -7.002 MME: -6.022 (0.980) QMD: 2.958 MMDistDelta: 0.000
> O2 QME: -4.205 MME: -4.749 (-0.544) QMD: 3.138 MMDistDelta: -0.100
> O3 QME: -4.819 MME: -6.231 (-1.412) QMD: 3.107 MMDistDelta: -0.200
> C QME: -1.277 MME: -1.662 (-0.385) QMD: 3.317 MMDistDelta: 0.200
> C2 QME: -2.221 MME: -0.399 (1.822) QMD: 3.065 MMDistDelta: 0.400
> C3 QME: -1.384 MME: -0.546 (0.839) QMD: 3.107 MMDistDelta: 0.400
> C4 QME: -1.087 MME: -1.957 (-0.870) QMD: 3.550 MMDistDelta: 0.100
> C5 QME: -0.352 MME: -1.431 (-1.080) QMD: 3.594 MMDistDelta: 0.000
> C7 QME: -0.316 MME: -0.990 (-0.674) QMD: 3.607 MMDistDelta: 0.050
> C9 QME: -0.991 MME: -1.217 (-0.226) QMD: 3.904 MMDistDelta: -0.100
> C10 QME: -1.348 MME: -1.305 (0.043) QMD: 4.313 MMDistDelta: 0.050
> C11 QME: -3.007 MME: -3.383 (-0.377) QMD: 3.445 MMDistDelta: 0.050
> C13 QME: 0.361 MME: -0.321 (-0.682) QMD: 4.635 MMDistDelta: -0.400
> C15 QME: 1.462 MME: 0.175 (-1.286) QMD: 3.591 MMDistDelta: 0.000
> C16 QME: 0.656 MME: -0.003 (-0.659) QMD: 3.641 MMDistDelta: 0.050
> H2 QME: -6.547 MME: -6.242 (0.305) QMD: 2.054 MMDistDelta: 0.100
> H3 QME: -7.646 MME: -7.617 (0.029) QMD: 1.949 MMDistDelta: 0.050
> H11 QME: -2.207 MME: -2.487 (-0.280) QMD: 2.430 MMDistDelta: 0.150
> H12 QME: -3.220 MME: -1.944 (1.276) QMD: 2.512 MMDistDelta: 0.350
> H QME: -0.868 MME: -1.303 (-0.435) QMD: 3.626 MMDistDelta: 0.100
> Dipole -- QM: {3.179 3.276 -0.308} (4.575 D) MM: {4.269 3.458 -0.635} (5.530 D) Ratio: 1.21
> Current objective value: 1007.140769 ( En: 514.390769 Dist: 492.750000 Dipole: 0.000000 )
>
>
> FINAL CHARGES
> C 0.082
> N -0.254
> C2 0.237
> N2 -0.251
> C3 0.238
> H 0.168
> O -0.428
> C4 -0.082
> H2 0.315
> C5 -0.030
> C6 -0.144
> H3 0.350
> C7 0.092
> O2 -0.392
> C10 0.257
> O3 -0.367
> C14 -0.133
> H11 0.157
> C15 0.123
> CL -0.122
> C16 -0.121
> H12 0.125
> END
>
> Be sure to check sum of charges for rounding errors!


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