Known issues and bugs (@striketeam)

Team members interested in following/pursuing/raising issues (please add yourself if you’re missed):

striketeam: @Chapin Cavender @Chris Ringrose @Christopher Bayly @Daniel Cole @David Dotson @David Mobley @Jeffrey Wagner @John Chodera @Josh Mitchell @Joshua Horton @Lee-Ping Wang @Lorenzo D'Amore @Matt Thompson @Michael Gilson @Michael Shirts @Pavan Behara @Tobias Huefner @Trevor Gokey@Lily Wang @Alexandra McIsaac

Time horizon: On-going

Goals

List of FF issues raised by internal/external members

Issue/task	Preliminary work/progress/comments	Status/Timeline	Notes

Issue/task	Preliminary work/progress/comments	Status/Timeline	Notes
Halogenated compounds Discussion link: https://openforcefieldgroup.slack.com/archives/CKSHCE7SB/p1611592728000200 Brief summary: Large discrepancies with experiment for the COVID Moonshot on compounds containing a chloro group on aromatic scaffolds	https://www.nist.gov/srd/refprop
Amide issue Discussion link: https://openforcefieldgroup.slack.com/archives/CKSHCE7SB/p1596485145006600 Brief summary: High preference to non-planar amides using Parsley 1.2.0	(wip)A fix of cic-trans preference of amides(for v1.3.1)
Problem chemistries from benchmark analysis by Thomas Fox, an industry partner. Additional analysis by Lorenzo D’Amore and Xavier Lucas Discussion link: https://openforcefieldgroup.slack.com/archives/C01BN0C5AKF/p1623935171007300 https://openforcefieldgroup.slack.com/archives/C01BN0C5AKF/p1623935450009200 https://openforcefield.atlassian.net/wiki/spaces/~954728248/pages/2110488578 https://openforcefieldgroup.slack.com/archives/C01BN0C5AKF/p1631634575020600 Brief summary: RMSD analysis of the QM minimum energy conformer and MM optimized conformer with 1.3.0	Observations of Thomas Fox: CC bond in oxirane 0.12A too long ("C1CO1") CC bond between the two C=O in quadratic acid 0.1A too long ("Oc1c(O)c(=O)c1=O") sulfoximide S=N bond 0.18A too long (Eg. "CCCCS(=N)(=O)CCC(N)C(O)=O") 2-vinyl-furan ("C=CC1=CC=CO1") is not planar aromatic nitro groups not in plane with ring (Eg. "C1=CC=C(C=C1)[N+](=O)[O-]") aromatic thioethers out of plane (Eg. "CSC1=CC=CC=C1") ring puckering of spiro-pyrrolidine (Eg. "C1CNCC12NC3=CC=CC=C3C(=O)N2") aryl-methoxy groups not planar (45°) (Eg. "COC1=CC=CC=C1") Disclaimer: added some smiles as a starting point/reference in case of general chemical space observations, may not be the exact molecules Thomas Fox is referring to when you see `Eg.`.	No action needed	Problem could not be reproduced with publically available molecules
Cyclobutane is flat (not puckered) with 1.2.0, 1.3.0.	QM in green above (from PhalkEtOH dataset) 1.2.0 in magenta above 1.3.0 in cyan above
Nitrogen-oxygen bonds in constrained systems (like rings) might result in long bonds with lengthy MM runs Discussion link: 2021-07-21 BespokeFit meeting notes	From Josh Horton’s lengthy MM run
Bicyclo pentane moieties difficult to converge with MM Discussion link: https://openforcefieldgroup.slack.com/archives/CK5MQG0TC/p1626985095050500
*t49 "~[#7a]:[#6a:3]~"* in Sage 2.1.- seems to be handled by later t84; should t49 be deleted? (raised by Paul Labute from CCG in a private email)	Redundant parameters in Sage 2.1 @Alexandra McIsaac	Completed	t49 is not redundant
*t123 "[:1]~[#15:2]-[#6:3]-[:4]"* in Sage 2.1.0 seems entirely contained in t123a and t124 - should t123 be deleted? The V1 value is suspicious too.	Redundant parameters in Sage 2.1 @Alexandra McIsaac	Completed	t123 is redundant (at least for the molecules in the training set)
*t164 "[:1]~[#7:2]=[#15:3]~[:4]"* in Sage 2.1.0 seems suspicious with V2 = -0.9671 which encourages 90 degrees. This can't be true for a true double bond between P and N (e.g.,C-P=N-C). This rule seems intended to cover CN=P(C)(C)C only. Is this true? If so, then #15X4 may be more appropriate.	Missing parameter coverage \| t164 @Brent Westbrook Only covered by 3 conformations of 1 molecule:	Completed	t164 needs way more training data
*t129 " [:1]-[#8X2r5:2]-;@[#7X2r5:3]~[:4]:"** in Sage 2.1.0 has a suspicious V = -19.907. Is this correct?	Redundant parameters in Sage 2.1 @Brent Westbrook	Completed	Reasonable for the training set, but may need more coverage in Sage 2.2
A rather more serious problem is with phosphorus parameters: *t159 "[:1]-[#8X2:2]-[#15:3]~[:4]"* 9.3828 0 -1.8998 0 0.4283 0 0.0000 0 0.0000 0.0000 t160 "[#8X2:1]-[#15:2]-[#8X2:3]-[#6X4:4]" 8.2041 0 -1.5697 0 -0.7592 0 0.0000 0 0.0000 0.0000 # t160 Are the phosphorus parameters are supposed to handle phosphines or just phosphates?	@Brent Westbrook t159 is covered 142 times in the sage 2.1.0 dataset, t160 is covered 74 times. To do: phosphine vs phosphates question
*t65 "[:1]-[#6X4:2]-[#7X3$(~[#8X1]):3]~[#8X1:4]"* should this be nitro [#7X3$:3](~[#8X1])~[#8X1:4]" like other similar rules or is nitroso also intended? If nitroso is intended then all you need is [*:1]-[#6X4:2]-[#7X3:3]~[#8X1:4]	As of Sage 2.1.0, t65 is trained on largely nitro groups but also additional N-O groups. However, it’s only benchmarked on nitro groups in the industry dataset, and its intention pretty clearly seems to be nitro applications. Changing it to the suggested SMARTS may be best here.
t77-t79 amide rules appear to encourage cis amides	Sage 2.1 t77-t79 cis amides
Systematic errors in parameters Brief summary: Many of our parameters seem to have either systematic errors (median error > 0) or sub-populations that suggest the parameter should be split	Systematic errors in parameters