This page contains an overview of the projects/studies aimed at improving the FF optimization process in general. Specific features and decisions made for each FF optimization cycle should be recorded in FF releases.

Objectives

Team

Main objective: Create general WBO interpolated parameters in the force field

Project driver: David Mobley Jessica Maat (Deactivated) Pavan Behara

Objectives for 2020:

Team members: David Dotson Jeffrey Wagner Chaya Stern (Deactivated) Trevor Gokey

Current Projects
Driver	Project / Study
Pavan Behara Trevor Gokey David Mobley Jessica Maat (Deactivated)	ForceBalance optimization of wiberg bond order interpolated parameters Analysis of QCA datasets for wbo versus torsion barrier height

Scientific Questions

Infrastructure Requirements
Desired features:	Software:

Action items

Experiment 3: Amide experiment Jessica Maat (Deactivated)

Review placement, and redundancy of parameters in iteration 5 (openff-1.3.0-tig-3.0), esp. closeness of parameters TIG* with t70-b,c,d - Jessica Maat (Deactivated)high priority

Review placement- check more general parameters are placed below a more specific parameter Jessica Maat (Deactivated)
Remove t70d, check if there are overlaps with t70* with any TIG*, add sulfur to TIG1c

Changed TIG1c from [*:1]~[#6X3:2](=[#8X1])~[#7X3,#7X2-1:3]~[*:4] to [*:1]~[#6X3:2](=[#8X1,#16X1])~[#7X3,#7X2-1:3]~[*:4], verify this change is correct with Pavan Behara
Create iteration 6

Do an initial fit with iteration 5(or 6) FF with Trevor's Help Pavan Behara

Check parameter coverage by incrementing datasets from Gen 2 sets (Gen 2 are used for fitting Parsley), suggest datasets for fitting - Pavan Behara
Pre-process datasets to tag molecules that overlap with Lim-Mobley_Benchmarking_set - Pavan Behara
Check params with negative slope (4, 5b) or possibility to split (6,7):
Outcome: The range of wbo values these parameters have in the plots is 0.2, so it is difficult to ascertain any specific behavior now. There doesn’t seem to be any chemical series that can separate them into more child parameters

TIG4, TIG5b Pavan Behara
TIG6, TIG7 Jessica Maat (Deactivated)

Pass FFs and targets to Trevor

Provide another FF to TG by splitting the interpolated params to single, aromatic, double bonded general torsion terms Pavan Behara
Analyze the outcome of the initial fits after getting back new FF from Trevor Pavan Behara

Plot QM Vs MM
Redo plots with MM_torsions vs WBO
Parameter specific gradients from Trevor’s work?

Plot the residuals (QM - MM_intrinsic_torsion), instead of current analysis solely done with QM data. - Jessica Maat (Deactivated)

David Dotson Pavan Behara Helping with the MM torsion barriers
David Dotson Pavan Behara Check in at 11 am
Jeffrey Wagner Joshua Horton Pavan Behara check in after ff-release call on MM intrinsic torsion

Fitting series of new interpolated torsion to a bunch of molecules with as much data in the plots as possible Pavan Behara Trevor Gokey

Refit just tig parameters, see if fitting only TIG parameters improve FF

By molecule fit, look at forcebalance repoJessica Maat (Deactivated)

Use ForceBalance to fit TIG0 for a single molecule/torsion profile with Parsley + TIG0

Pick a molecule
Prep FFXML file for FB
Prep targets for FB
run FB
Evaluate results: Check objective function before and after
Evaluate results: check torsion profile before and after and compare to QM

Iterate over many molecules and fit new TIG0 for each, storing k values by molecule (with sub-tasks

pick molecules to iterate over
iterate and fit using FB
evaluate results for each

Generate new plot of k vs WBO, where now we plot k from the fits out of TIG0

Only include molecules without strong steric clashes (LJ) in this analysis
break out molecules by TIGn parameter which WOULD be applied (even though all k values come from TIG0)

Repeat experiment [*:1]~[#6X3:2]~[#7:3]~[*:4]
Splitting parameters based on K versus WBO
Generate unique smirks pattern for torsion

Two experiments:

Fitting series of new interpolated torsion to a bunch of molecules with as much data in the plots as possible Pavan Behara Trevor Gokey
By molecule fit, look at forcebalance repo Jessica Maat (Deactivated)

ForceBalance runs on WBO Interpolated Parameters

The substituted phenyl dataset parameter usage using OpenFF v1.3.0 for Rowley and Phenyl Datasets:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.41.18 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 12.34.19 PM.png

The substituted phenyl dataset parameter usage using FF with only proposed interpolated parameters for Rowley and Phenyl Datasets:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.37.32 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-28 at 9.57.20 AM.png

The Phenyl dataset parameter usage using FF with only proposed TIG interpolated parameters for Rowley and Phenyl Datasets:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.36.49 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 1.39.36 PM.png

The Phenyl dataset parameter usage using FF with only proposed it1-7 interpolated parameters for Rowley and Phenyl Datasets:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.30.52 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-28 at 10.17.18 AM.png

Proposed WBO interpolated parameters from Chris Bayly:

General parameters:

TIG0 [*:1]~[#6X3:2]~[#6X3:3]~[*:4]

TIG1 [*:1]~[#6X3:2]~[#7X3:3]~[*:4]

TIG2 [*:1]~[#6X3:2]~[#7X2:3]~[*:4]

TIG3 [#6X3:1]~[#6X3:2]~[#6X3:3]~[*:4]

TIG4 [#7X2:1]~[#6X3:2]~[#6X3:3]~[*:4]

TIG5 [#7X3#8X2#16X2:1]~[#6X3:2]~[#6X3:3]~[*:4]

TIG6 [#6X3:1]~[#6X3:2]~[#7X3:3]~[*:4]

TIG7 [#7X2:1]~[#6X3:2]~[#7X3:3]~[*:4]

TIG8 [#7X3#8X2#16X2:1]~[#6X3:2]~[#7X3:3]~[*:4]

    <Proper smirks="[*:1]~[#6X3:2]~[#6X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG0" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]~[#7X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG1" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]~[#7X2:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG2" idivf1="1.0"></Proper>
    <Proper smirks="[#6X3:1]~[#6X3:2]~[#6X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG3" idivf1="1.0"></Proper>
    <Proper smirks="[#7X2:1]~[#6X3:2]~[#6X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG4" idivf1="1.0"></Proper>
    <Proper smirks="[#7X3,#8X2,#16X2:1]~[#6X3:2]~[#6X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG5" idivf1="1.0"></Proper>
    <Proper smirks="[#6X3:1]~[#6X3:2]~[#7X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG6" idivf1="1.0"></Proper>
    <Proper smirks="[#7X2:1]~[#6X3:2]~[#7X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG7" idivf1="1.0"></Proper>
    <Proper smirks="[#7X3,#8X2,#16X2:1]~[#6X3:2]~[#7X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG8" idivf1="1.0"></Proper>

Parameters for substituted phenyl dataset:

TIG9 [*:1]~[#6X3:2]-[#7X3:3]-[#6X4#1:4]

TIG10 [*:1]~[#6X3:2]-[#8X2:3]-[#6X4#1:4]

TIG11 [*:1]~[#6X3:2]-[#7X3:3]-[#6X3:4]=O

TIG12 [*:1]~[#6X3:2]-[#8X2:3]-[#6X3:4]=O

TIG13 [*:1]~[#6X3:2]-[#7X3:3](~[#8X1])[#8X1:4]

TIG14 [*:1]~[#6X3:2]-[#6X3:3](-[#8H1])=[#8X1:4]

TIG15 [*:1]~[#6X3:2]-[#6X3:3](~[#8X1])[#8X1:4]

    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3]-[#6X4,#1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG9" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#8X2:3]-[#6X4,#1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG10" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3]-[#6X3:4]=O" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG11" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#8X2:3]-[#6X3:4]=O" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG12" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3](~[#8X1])[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG13" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#6X3:3](-[#8H1])=[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG14" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#6X3:3](~[#8X1])[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG15" idivf1="1.0"></Proper>

Experiment 1: Adding TIG1-8, general WBO interpolated parameters to OpenFF v1.3.0:

Workflow:

Start with TIG0 parameter
Add parameter to FF hierarchy using the results from FF’s using only interpolated parameters and inspection of current FF parameters
Generate the parameter usage plots for phenyl and Rowley dataset
Compare plot to the parameter usage results using only interpolated parameters to make sure usage is reasonable
Move to next parameter, and repeat at step #1 until all parameters are added to FF

Experiment Notes:

General WBO Interpolated Parameters

SMIRKS

Insertion in v1.3.0 OpenFF

TIG0

[*:1]~[#6X3:2]~[#6X3:3]~[*:4]

Iteration 5: No change

Replace t43-t45

After addition to TIG0:

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 12.27.21 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 12.27.27 PM.png

Iteration 5:

Plot of TIG0 over all QCA data, only one point left after being drained by specific parameters that come after this

Force Fields > WBO Interpolated Parameters > image-20201111-213003.png

TIG1

Iteration 1: [*:1]~[#6X3:2]~[#7X3:3]~[*:4]

Iteration 2: [*:1]~[#6X3:2]~[#7X3, #7X2-1:3]~[*:4]

Iteration 4,5:

TIG1a [*:1]~[#6X3:2]@[#7X3,#7X3+1,#7X2,#7X2-1:3]~[*:4]

TIG1b [*:1]~[#6X3:2]@[#6X3:3]~[*:4]

TIG1c [*:1]~[#6X3:2](=[#8X1])~[#7X3,#7X2-1:3]~[*:4]

TIG1d [*:1]~[#6X3:2](~[#7X2])~[#7X3,#7X2-1,#7X2,#7X3+1:3]~[*:4]

Iteration 1:

Below t69 and t69a

Question:

-Should we replace t69 parameters with TIG1?

The parameters t69 and t69a:

    <Proper smirks="[*:1]~[#7X3,#7X2-1:2]-!@[#6X3:3]~[*:4]" periodicity1="2" phase1="180.0 * degree" k1="1.624344674592e+00 * mole**-1 * kilocalorie" id="t69" idivf1="1.0"/>
    <Proper smirks="[*:1]-[#7X3:2]-[#6X3$(*=[#8,#16,#7]):3]~[*:4]" periodicity1="2" periodicity2="1" phase1="180.0 * degree" phase2="0.0 * degree" k1="1.802103402795e+00 * mole**-1 * kilocalorie" k2="0.0 * mole**-1 * kilocalorie" id="t69a" idivf1="1.0" idivf2="1.0"/>

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 12.32.27 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 12.32.33 PM.png

Iteration 2 based on suggestions from David Mobley :

Change tig0 to [*:1]~[#6X3:2]~[#7X3, #7X2-1:3]~[*:4]
Replace t69 with tig0

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.10.02 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.09.57 PM.png

Iteration 5:

TIGs a and b correspond to ring torsions that correlate with high barriers and are placed at the bottom after t83

TIG1c and TIG1d are splits of TIG1 into two chemical series:

(1) carbonyl with a nitrogen and

(2) Formamidine type molecules

Force Fields > WBO Interpolated Parameters > image-20201109-171917.png

Force Fields > WBO Interpolated Parameters > image-20201109-173207.png

After splitting to 1c and 1d, and placing 1d after TIG2 here are the plots:

Force Fields > WBO Interpolated Parameters > image-20201111-203717.png

Force Fields > WBO Interpolated Parameters > image-20201111-203829.png

TIG2

Iteration 1: [*:1]~[#6X3:2]~[#7X2:3]~[*:4]

Iteration 2: [*:1]~[#6X3:2]~[#7X2, #7X3+1:3]~[*:4]

Iteration 5: No change

Iteration 1:

After t80, which is the most specific parameter with “[#6X3:2] [#7X2:3]”

*No change in plots from TIG1 experiment, was expected because Rowley and Phenyl dataset do not use TIG2 in experiment with only interpolated params.

Iteration 2 based on feedback from David Mobley:

Generalize parameter to [*:1]~[#6X3:2]~[#7X2, #7X3+1:3]~[*:4]
Replace t76-78 with tig2

Substituted phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.28.20 PM.png

Rowley dataset:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.28.16 PM.png

*TIG2 is capturing a chemical series that t72 used to capture, this looks much better than previous parameter placement.

Iteration 5:

Plot of TIG2 over all QCA data

Force Fields > WBO Interpolated Parameters > image-20201111-204132.png

TIG3

[#6X3:1]~[#6X3:2]~[#6X3:3]~[*:4]

Iteration 5: No change

Replace t48 with TIG3

Parameter t48 is a more specific child parameter of TIG3:

<Proper smirks="[#6X3:1]=[#6X3:2]-[#6X3:3]=[#8X1:4]" periodicity1="2" periodicity2="3" phase1="180.0 * degree" phase2="0.0 * degree" k1="3.980018770084e-01 * mole**-1 * kilocalorie" k2="-3.9 38620201049e-01 * mole**-1 * kilocalorie" id="t48" idivf1="1.0" idivf2="1.0"/>

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 1.39.01 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 1.38.56 PM.png

Experiment proposal from David Mobley :

Retain t48 below TIG3 and (maybe) add interpolation.
Run this experiment in fitting, or see how (once you have more data on this plots) it would separate things.

Iteration 5:

Plot of TIG3 over all QCA data

Force Fields > WBO Interpolated Parameters > image-20201111-204221.png

TIG4

[#7X2:1]~[#6X3:2]~[#6X3:3]~[*:4]

Iteration 5: [#7X2:1]@[#6X3:2]~[#6X3:3]@[*:4]

After TIG3 parameter, which is the closest parameter to TIG4.

There are no obvious parameters in the FF that TIG4 could replace, t40 is closest but too far up in the hierarchy. This would make TIG4 come before TIG0 and so on.

t40 parameter:

    <Proper smirks="[#6X4;r3:1]-;@[#6X4;r3:2]-[#6X3:3]=[#7X2:4]" periodicity1="3" periodicity2="2" periodicity3="1" phase1="0.0 * degree" phase2="180.0 * degree" phase3="180.0 * degree" k1="-3.973437766056e-01 * mole**-1 * kilocalorie" k2="1.595780918938e+00 * mole**-1 * kilocalorie" k3="1.436787426846e-01 * mole**-1 * kilocalorie" id="t40" idivf1="1.0" idivf2="1.0" idivf3="1.0"/>

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.47.46 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.47.51 PM.png

Iteration 5:

When this parameter is plotted over all QCA data some molecules not grouped with others make the slope negative. ~~Making this parameter more specific to biaryl kind of molecules alleviates this problem.~~ After adding the data from ‘OpenFF Group 1 Torsions’ we still see a downtrend for this parameter

Force Fields > WBO Interpolated Parameters > image-20201111-211326.png

TIG5

[#7X3, #8X2, #16X2:1]~[#6X3:2]~[#6X3:3]~[*:4]

Iteration 5:

TIG5a [#7X3,#8X2,#16X2:1]~[#6X3:2]~[#6X3:3](=[#8X1])~[*:4]

TIG5b [#7X3,#8X2,#16X2:1]@[#6X3:2]~[#6X3:3]@[*:4]

TIG5 was placed after TIG4, these parameters cover chemistries of sp2 carbon-carbon bonds.

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.54.02 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 2.54.07 PM.png

Iteration 5:

Similar to TIG1 split, here also dividing into two parameters that correspond to

(1) Carbonyls with a side carbon

(2) biaryl or an aryl on one side and a dangling chain on other side of the central bond

Force Fields > WBO Interpolated Parameters > image-20201109-175454.png

Post split the plots are:

5a on left, 5b on the right

Force Fields > WBO Interpolated Parameters > image-20201111-211439.png

Force Fields > WBO Interpolated Parameters > image-20201111-225031.png

TIG6

Iteration 1: [#6X3:1]~[#6X3:2]~[#7X3:3]~[*:4]

Iteration 2: [#6X3:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]

Iteration 5: No change

Iteration 1:

After t78, there are a lot of parameters that cover #7X3 - #6 chemistry.

It’s unclear if any parameters should be replaced by these.

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.08.14 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.08.21 PM.png

*If this plot were to perfectly reproduce the ff with only the TIG parameters, we should see only TIG3, 5, and 6 in this plot. There are also t96 and t97.

This might be an indication that the parameter placement is not correct, or t96 or t97 need an interpolated parameter.

Iteration 2 proposed by David Mobley :

Change parameter to [#6X3:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]
Place tig6 after tig1

Rerunning the parameter assignment plots with tig6 iteration 2 in openff-1.3.0-tig.offxml modified:

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.48.34 PM.png

Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.48.29 PM.png

Iteration 5:

Plot of TIG6 over all QCA data

Force Fields > WBO Interpolated Parameters > image-20201111-211626.png

TIG7

Iteration 1: [#7X2:1]~[#6X3:2]~[#7X3:3]~[*:4]

Iteration 2: [#7X2:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]

Iteration 1:

After TIG6.

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.17.54 PM.png

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.17.59 PM.png

Iteration 2:

Placed after tig6 still, but tig6 is moved in the FF as outlined above
Parameter changed to: [#7X2:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]

Rerunning the parameter assignment plots with tig7 iteration 2 in openff-1.3.0-tig.offxml modified:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.54.16 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.54.20 PM.png

Iteration 5:

Plot of TIG7 over all QCA data

Force Fields > WBO Interpolated Parameters > image-20201111-211758.png

TIG8

Iteration 1: [#7X3,#8X2,#16X2:1]~[#6X3:2]~[#7X3:3]~[*:4]

Iteration 2: [#7X3,#8X2,#16X2:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]

Iteration 5: [#7X3,#8X2,#16X2:1]@[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]

Iteration 1:

TIG8 placed after TIG7.
Parameters TIG6-8 are in a similar hierarchy.

Rowley DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.26.24 PM.png

*exactly reproduces FF results from using only TIG parameters

Substituted Phenyl DS:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-27 at 3.26.30 PM.png

*Same case as prior with t96 and t97

Iteration 2:

Parameter changed to [#7X3,#8X2,#16X2:1]~[#6X3:2]~[#7X3,#7X2-1:3]~[*:4]
Placed after new placement of tig7

Rerunning parameter assignment:

Rowley:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.58.21 PM.png

Phenyl:

Force Fields > WBO Interpolated Parameters > Screen Shot 2020-10-29 at 1.58.15 PM.png

Iteration 5:

Making TIG8 more specific to capture biaryl or bridged-aryl type of molecules. Plot below for the entire QCA torsiondrive datasets.

Force Fields > WBO Interpolated Parameters > image-20201111-212853.png

1. This is the resulting FF from the prior experiment:

2. 2nd Iteration resulting FF from the prior experiment:

3. 3rd iteration, addition of TIG1a covering ring chemistry, openff-1.3.0-tig-2.0

4. 4th iteration, TIG1a after t83 and remove t69a, openff-1.3.0-tig-2.2

5. 5th iteration, parameter splits or making parameters more specific based on chemical series, openff-1.3.0-tig-3.0

Iteration 4 FF plots here
https://docs.google.com/presentation/d/1dOUi9zz5UvWOUVLmu-KqcfH3KGay_NDTq7bIaMZ7LGk/edit?usp=sharing
Iteration 5 plots and chemical series analysis here
https://docs.google.com/presentation/d/1tqWBj_5TmtHuR77VkdZ1wQ0Y6eEbRx64hU5XcWWzqp0/edit?usp=sharing

Experiment 2: Adding TIG9-15, general WBO interpolated parameters to OpenFF v1.3.0:

    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3]-[#6X4,#1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG9" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#8X2:3]-[#6X4,#1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG10" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3]-[#6X3:4]=O" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG11" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#8X2:3]-[#6X3:4]=O" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG12" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#7X3:3](~[#8X1])[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG13" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#6X3:3](-[#8H1])=[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG14" idivf1="1.0"></Proper>
    <Proper smirks="[*:1]~[#6X3:2]-[#6X3:3](~[#8X1])[#8X1:4]" periodicity1="2" phase1="180.0 * degree" k1_bondorder1="1*kilocalories_per_mole" k1_bondorder2="10*kilocalories_per_mole" id="TIG15" idivf1="1.0"></Proper>


TIG9	[*:1]~[#6X3:2]-[#7X3:3]-[#6X4#1:4]	After t78 *Rowley & phenyl DS same as openff 1.3.0 Phenyl DS:
TIG10	[*:1]~[#6X3:2]-[#8X2:3]-[#6X4#1:4]
TIG11	[*:1]~[#6X3:2]-[#7X3:3]-[#6X3:4]=O
TIG12	[*:1]~[#6X3:2]-[#8X2:3]-[#6X3:4]=O
TIG13	[*:1]~[#6X3:2]-[#7X3:3](~[#8X1])[#8X1:4]
TIG14	[*:1]~[#6X3:2]-[#6X3:3](-[#8H1])=[#8X1:4]
TIG15	[*:1]~[#6X3:2]-[#6X3:3](~[#8X1])[#8X1:4]

Summary of number of overlaps for different datasets with Lim Mobley Benchmark set:

Fragment Stability Benchmark: 0
OpenFF Fragmenter Validation 1.0: 3
OpenFF Full TorsionDrive Benchmark 1: 56
OpenFF Gen 2 Torsion Set 1 Roche 2: 3
OpenFF Gen 2 Torsion Set 2 Coverage 2: 0
OpenFF Gen 2 Torsion Set 3 Pfizer Discrepancy 2: 39
OpenFF Gen 2 Torsion Set 4 eMolecules Discrepancy 2: 209
OpenFF Gen 2 Torsion Set 5 Bayer 2: 0
OpenFF Gen 2 Torsion Set 6 Supplemental 2: 0
OpenFF Group1 Torsions 2: 0
OpenFF Group1 Torsions 3: 0
OpenFF Primary Benchmark 1 Torsion Set: 238
OpenFF Primary Benchmark 2 Torsion Set: 400
OpenFF Primary TorsionDrive Benchmark 1: 10
OpenFF Rowley Biaryl v1.0: 0
OpenFF Substituted Phenyl Set 1: 1
OpenFF-benchmark-ligand-fragments-v1.0: 1
Pfizer Discrepancy Torsion Dataset 1: 56
SMIRNOFF Coverage Torsion Set 1: 0
TorsionDrive Paper: 0

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ForceBalance runs on WBO Interpolated Parameters

Experiment 1: Adding TIG1-8, general WBO interpolated parameters to OpenFF v1.3.0:

Workflow:

Experiment Notes:

1. This is the resulting FF from the prior experiment:

2. 2nd Iteration resulting FF from the prior experiment:

3. 3rd iteration, addition of TIG1a covering ring chemistry, openff-1.3.0-tig-2.0

4. 4th iteration, TIG1a after t83 and remove t69a, openff-1.3.0-tig-2.2

5. 5th iteration, parameter splits or making parameters more specific based on chemical series, openff-1.3.0-tig-3.0

Experiment 2: Adding TIG9-15, general WBO interpolated parameters to OpenFF v1.3.0: