0.
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Torsion profile of amide bond of N-methylacetamide using v1.2.0 fails to reproduce QM torsion profile, forming a small hump at the minimum. Re-fitting to the selected torsion targets which rotate an amide bond couldn’t remove the hump.
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So one easy fix of the problem is using simple targets which behave exactly as we expect near the minimum (planar amide bond at the minimum) and here’s what I did:
1.
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Filtering non-planar structure at minimum geometry
since the 2nd generation torsion training set is too small to filter, i pulled Roche torsion set (1st gen) and filtered with various scheme.
scheme 1. check improper dihedral angle of input.mol2 (which is generated using openeye toolkits) take targets whose C-center and N-center improper dihedral angles are both between -5.0, 5.0 degree;scheme 2. check improper dihedral angles at the minimum energy point of the torsion profile, take targets whose C-center and N-center improper dihedral angles are both between -5.0, 5.0 degree;
scheme 3. check QM data to see if the profile has its local minima at 0 or 180;
scheme 4. targets passed either scheme 2 or scheme 3
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2. fb-fit2 vs fb-fit2-2
SMIRKS | initial guess | fb-fit2 | fb-fit4 | |
|---|---|---|---|---|
t69a | [*:1]-[#7X3:2]-[#6X3$(*=[#8,#16,#7]):3]~[*:4] | 2.5 (1+cos(2x-180)) | 2.5 (1+cos(2x-180)) | 2.516923679597e+00(1+cos(2x-180)) |
t69b | [*:1]-[#7X3:2]-!@[#6X3$(*=[#8,#16,#7]):3]~[*:4] | 2.5 (1+cos(2x-180)) | 1.652160092455e+00 (1+cos(2x-180)) | 1.799860521668e+00(1+cos(2x-180)) |
t70 | [#1:1]-[#7X3:2]-[#6X3:3]=[#8,#16,#7:4] | 3.459249459574e+00 (1+cos(2x-180)) + 1.356955617521e+00 (1+cosx) | 3.459249459574e+00 (1+cos(2x-180)) + 1.356955617521e+00 (1+cosx) | 3.458787578663e+00(1+cos(2x-180)) + 1.357031068121e+00(1+cosx) |
t70a | [#1:1]-[#7X3:2]-!@[#6X3:3]=[#8,#16,#7:4] | 2.5 (1+cos(2x-180)) + 2.0 (1+cosx) | -2.081991778915e-01 (1+cos(2x-180)) + 1.400460484703e+00 (1+cosx) | -1.615997113282e+00(1+cos(2x-180)) + 1.289607014774e+00(1+cosx) |
t70b | [*:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1] | 2.5 (1+cos(2x-180)) | 4.091207931356e+00 (1+cos(2x-180)) | 4.079468007826e+00(1+cos(2x-180)) |
t70c | [#1:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1] | 2.5 (1+cos(2x-180)) + 2.0 (1+cosx) | 1.301446828323e+00 (1+cos(2x-180)) + 9.476830965983e-01 (1+cosx) | 1.020531593037e+00(1+cos(2x-180)) + 7.399229872960e-01(1+cosx) |
t70d | [*:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#7X3] | 2.5 (1+cos(2x-180)) | 1.271374777009e+00 (1+cos(2x-180)) | 1.142115082029e+00 (1+cos(2x-180)) |
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Although the k1 value for t70a seems unphysical, the result below shows the plots got improved after the optimization. checked improvement for all of the four fitting targets.
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3. fb-fit4 vs fb-fit4-2
SMIRKS | initial guess | fb-fit2-2 | fb-fit4-2 | |
|---|---|---|---|---|
t69a | [*:1]-[#7X3:2]-[#6X3$(*=[#8,#16,#7]):3]~[*:4] | 2.5 (1+cos(2x-180)) | 1.679285484776e+00 (1+cos(2x-180)) | 1.778613695219e+00(1+cos(2x-180)) |
t70 | [#1:1]-[#7X3:2]-[#6X3:3]=[#8,#16,#7:4] | 3.459249459574e+00 (1+cos(2x-180)) + 1.356955617521e+00 (1+cosx) | 3.566161051804e-01 (1+cos(2x-180)) + 1.354248559088e+00 (1+cosx) | -1.357682774067e+00 (1+cos(2x-180)) + 1.266337423993e+00 (1+cosx) |
t70b | [*:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1] | 2.5 (1+cos(2x-180)) | 4.169159533591e+00 (1+cos(2x-180)) | 4.107144298045e+00(1+cos(2x-180)) |
t70c | [#1:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1] | 2.5 (1+cos(2x-180)) + 2.0 (1+cosx) | 1.240609067243e+00 (1+cos(2x-180)) + 9.065552775144e-01 (1+cosx) | 1.115929833406e+00(1+cos(2x-180)) + 7.646525300953e-01(1+cosx) |
t70d | [*:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#7X3] | 2.5 (1+cos(2x-180)) | 1.303139175986e+00 (1+cos(2x-180)) | 1.167960735598e+001+cos(2x-180)) |
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v1.2.0 | fb-fit2 | fb-fit2-2 | fb-fit4 | fb-fit4-2 | |
|---|---|---|---|---|---|
test cal. | 144.59 | 90.79 | 91.81 | 88.54 | 88.84 |
final obj. fn. (fitting) | - | 1.38e+02 → 2.21e+01 | 1.31e+02 → 2.22e+01 | 2.16e+02 → 2.95e+01 | 2.09e+02 → 3.01e+01 |
4.
* Fitting torsion parameters to simpler torsion targets (with less strong electrostatic interaction) might be needed for the next round fitting.