summary (~1/6)

1. Issue with amide cic-trans preference

Cis-trans preference is expressed as a one-fold cosine function in torsion term. To properly describe cis-trans preference of N-methyl acetamide, the k2 value(spring constant of one-fold cosine function. f(theta)= k1*(1+cos(2*theta-180)) + k2*(1+cos(1*theta))) of t70c([#1:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1]) seems to be around 1.5 kcal/mol.

Open

Initial guess of the k2 is 2.0kcal/mol, which seems a pretty reasonable value, but it decreases during the fitting to QM amide torsional energy profiles. (in fitting v1.3.0)

Open

To figure out the origin of the decrease in the k2 value of t70c([#1:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1]), gradient contribution at the initial guess has been plotted.

QM energy profiles of the targets with the most negative gradient contribution w.r.t the t70c k2 value show the energy gap between cis and trans conformers are much smaller(close to zero) than other amides. Therefore, separating those from t70c might be able to allow t70c to have large enough k2 value, so that it can keep the t70c term from losing its cis trans preference. So i came up with the new child parameter of t70, t70e and ran test fitting to see the impact of the additional parameters.

…

(2) RC6

• param modification:

  • t70e [#1:1]-[#7X3:2](-[#6X3](-@[#8,#16]))-!@[#6X3:3](=[#8,#16,#7:4])-[#6,#1] (between t70c and t70d)

  • t70f [#1:1]-[#7X3:2]-!@[#6X3:3](=[#8,#16,#7:4])-[#7X3] (after t70d)

• resulting parameters:

• Separation of the first two rotations(no significant cis-trans preference) and the last molecule into different parameter shows improvement in cis-trans preference predictions.

* Diverse functional groups in the amide nitrogen side