Science Roadmap 2020

This scientific roadmap includes the next two planned force field releases and a list of scientific studies which need to be performed in 2020. Each study has a priority assigned to it. This roadmap can be continuously updated, but the overall status and priorities will be revised and updated in June 2020.

Force Fields

Upcoming force field versions:

Version	Codename	Features	Expected release date	Comment / Blocker

Version

Codename

Features

Expected release date

Comment / Blocker

openff-1.2.0

Parsley

Redesigned QM dataset for parameterization with better/broader coverage
Parameter fixes

Expected: May 2020

Released: Jun 3, 2020

openff-1.3.0

Parsley

Improvements to priors by element, etc., allowing for more accurate fitting
Filtering of molecules used in fitting certain torsions (esp. for amides) to improve parameter quality (came up in the progress of fixing a problem elsewhere)
Discussed in this release call: 2020-09-17 FF Release Meeting notes

When ready. September-December 2020.

openff-2.0.0

Sage

LJ refit (based on the ongoing feasibility study)
Limited WBO torsion interpolation for systems for which data already exists (more torsional data needed for a wide range application)

Exepected: Release date to be set by November 2020 and will have three month lead time. Likely release between December 2020 and Feb. 2021.

How fast can we do WBO interpolations (Pavan)
@Simon Boothroyd needs to get in touch with @David Hahn and folks from the Chodera lab to discuss some free energy benchmarking after LJ fitting
Late 2020/early 2021 still feasible

Scientific studies

The list of scientific studies which need to be performed in 2020, which will be updated every 3 months, as suggested in the science project management workflow. Each study should be linked to its Confluence page with more information about study design, execution and results. The study design should be submitted before study is about to begin.

Estimate start dates and end dates when possible before study has started. Record the real start and end dates for each study below the estimated dates.

Labels

Category	Labels

Category	Labels
Priority	high \| MEDIUM \| LOW
Effort	high \| MEDIUM \| LOW
Status	Not started \| In Progress \| PROTOTYPE \| Completed \| BLOCKED \|

Study	Priority	Effort	Science dependencies	Infrastructure dependencies	Comment	Start date	End date	Status	Driver/Team
Chemical perception
Addition of new parameters – manually fixing problems	high	high		Made easier by benchmarking dashboard (Optional)	Made easier by benchmarking dashboard (Optional			in progress	@Hyesu Jang @David Mobley @Jessica Maat (Deactivated) @Victoria Lim (Deactivated)
Automated typing inference from scratch	Medium	high			Organise a meeting to coordinate efforts. Update: @Tobias Huefner is doing some basic research, but we don’t have a timeline defined here. Perhaps a more specific study to look at typing issues similar to Schauperl’s work on LJ typing.			in progressSlowly	Full-time person needed – to be discussed further. Work of @Josh Fass (Deactivated) and @Tobias Huefner may assist here. @Owen Madin interested. @Trevor Gokey is also actively working in this area.
Mixture Properties
Binary Mixture Data Feasibility Study	high				In the writing stage.			COMPLETED	Driver: @Simon Boothroyd Team: @Michael Shirts @Owen Madin
Non-bonded optimization	high	high			Parent study for in a long-term progress stage.			in progress	Driver:@Simon Boothroyd Team: @Michael Shirts @Owen Madin
Chemical potential-like properties	MEdium		Non-bonded optimization	Implementation in `Evaluator`	Need to evaluate the data first (testing needed). Add Confluence page here.			In Progress PROTOTYPE	@Simon Boothroyd spinoff
Solvent-solvent partition coefficients	MEdium			Implementation in `Evaluator`	Data needed, harder problem. Update: Access to solubility phase, data is less of a problem now (MNSOL)			not started	@Simon Boothroyd spinoff
Data coverage and availability	high		Feasibility studies		Check the available data and identify missing data points. Worry in the future what to do about it. We will use what we have for Sage.			Ongoing	@Simon Boothroyd @Owen Madin @Michael Shirts
QM Data Generation
QM Data Selection (training data) for OpenFF-1.2.0	high				Need to expand to benchmarking set.			completed	@David Mobley @Jessica Maat (Deactivated) @Hyesu Jang
QM dataset selection for OpenFF-2.0.0	high							in progress	@David Mobley @Jessica Maat (Deactivated) @Hyesu Jang Lead: @Hyesu Jang ??
Benchmarking/re-evaluating our choice of QM theory	high			(Optional) QC Dataset submission infrastructure	Test of the whole torsiondrive. Keep within 10-50 torsiondrives. More is better. Some datasets ready, but analysis is still required (@Hyesu Jang ) Pavan might help with this. No changes made to our fitting data til after 2.0 release, but decision may be made before that (eg while fitting)			in progress	@Hyesu Jang lead; @Lee-Ping Wang @Pavan Behara @Hyesu Jang also leading molecule set selection with help from @Jessica Maat (Deactivated) and @Victoria Lim (Deactivated)
Protomer/tautomer enumerated molecules	high		QM level of theory validation (QMLoTV)	Protonation/tautomer enumeration integration (@Joshua Horton doing OE version in toolkit; there’s currently no good protonation state enumeration with RDKit – see )	It can only do enumeration with OpenEye			PRototyped	@Joshua Horton
Data selection for ionic species					What kind of experimental data would we need to include charged molecules?			NOt started	Lead: @Simon Boothroyd (oversight, to assemble team?)
Data on molecules with nonzero formal charges	high		QM level of theory validation (QMLoTV)	(Optional) QC Dataset submission infrastructure	Couples to benchmarking			NOt started	@Pavan Behara
Enamine REAL fragment coverage	MEDIUM			Automated fragmentation integration @Joshua Horton				in progress	@Trevor Gokey
Ligand Expo fragment coverage	MEDIUM			Automated fragmentation integration @Joshua Horton	Ligand Expo has higher priority than Enamine Real.			NOT started
Richer torsion data for WBO fitting	Low			WBO torsion implementation	What data to generate and				(person needed to continue work of @Chaya Stern (Deactivated); Will be @Pavan Behara with @Jessica Maat (Deactivated) , eventually coordinating with @Simon Boothroyd as he moves to his new position. )
Biopolymer data selection (ensure sidechain data is available in QCA)	high				One dataset ready, but a lot more data needs to be generated if we want sidechain sampling			in progress	@David Cerutti (Deactivated)
Biopolymer data computation	MEDIUM			(Optional) QC Dataset submission infrastructure				in progress	@David Cerutti (Deactivated) @David Dotson
More efficient torsion sampling with less grid points during scan	Low								spinoff
Fitting
Addition of new parameters – manually fixing problems	high	high				Ongoing		in progress	@Hyesu Jang @David Mobley @Jessica Maat (Deactivated) @Victoria Lim (Deactivated)
LJ refitting (Sage)	high		Non-bonded optimization					in progress	@Simon Boothroyd and @Owen Madin
WBO refitting (Sage)	high		More torsion data	WBO torsion implementation: Done.	Implement what Chaya has already done. Infrastructure ready. @Pavan Behara and @Jessica Maat (Deactivated) to divide up chemical space for fitting/test fixes. @Hyesu Jang will do central fitting of production FF. Additional discussion: https://openforcefield.atlassian.net/wiki/spaces/OFFO/pages/670629936/90-day+plan+Onboarding+for+Pavan+Behara?accessType=view&grantAccess=true&username=5f592e4d0b6be2006ef56679&userFullName=Pavan%20Behara#Notes-from-9%2F16%2F20-planning-meeting-(feel-free-to-migrate)	After May meeting	Late 2020 (Sep 2020)	in progress	@Jessica Maat (Deactivated) and @Pavan Behara . @Pavan Behara will eventually oversee.
BCC refitting	high		LJ refit Patterns for BCCs; could start with something simple like bond SMARTS.	ChargeIncrementModel implementation (early May)				in progress	@Simon Boothroyd @Owen Madin
Study how to set prior widths and weights for different sorts of data during FF optimization	medium				Became higher priority due to need for fixes. Headed towards a 1.3 release late 2020.			in progress	@Lee-Ping Wang @Hyesu Jang Spinoff?
Value of data generated “incidentally” during torsiondrive in fitting, e.g. optimization snapshots, gradients, energies (low control over these data points)	Low			Some parts of OpenFF Bespokefit	Once we have more people working on fitting, someone can run this study				@Joshua Horton spinoff
Benchmarking
Small reference system for fast testing of FE infrastructure – 5-10 small reference systems, possibly subset of SAMPL challenges, for comparison of different free energy methods to avoid using large P-L systems for test calculations	Low	Low			Should use SAMPLing challenge systems plus a couple more similar ones.		ASAP	Not started
Benchmarking/re-evaluating our choice of QM theory	high	medium			See above; to be done while fitting 2.0 (datasets ready). @Hyesu Jang leading.			Not started	@Lee-Ping Wang @Hyesu Jang @Pavan Behara
CCDC data selection/release	Low								spinoff
Create a list of tests to judge the “quality” of biopolymer FF with our scientific advisory board	HIGH				Organise the meeting with our IAB, invite to May meeting. Done. DC and MS will start conversations to get this going.		April / May	in progress	@David Cerutti (Deactivated) @Michael Shirts
`openff-1.2.0` (Parsley) benchmarking			Minor release of Parsley	Benchmarking dashboard	Done in preprint form, but no benchmarking dashboard. Still need torsion benchmarking; utilize work just done for OpenFF 1.0 paper. JDC is trying to get a complete FE set run by D. Rufa.		Mid 2020	Done-ish
`openff-2.0.0` (Sage) benchmarking			Release of Sage	Benchmarking dashboard			Late 2020	Not started
Biopolymers
Which quantum method should we use for biopolymers (should it be the same as small molecules)?	medium		QM benchmarking study		Short term – using the same method and same level of theory as ANI (wB97D)			Not started	@Lee-Ping Wang @David Cerutti (Deactivated)
Feasibility/benchmarking studies of torsional CMAPs	medium		After protein FF implementation	CMAP support in OFFTK				Not started	@David Cerutti (Deactivated)
Feasibility/benchmarking studies of other cross-terms	Low			Support for cross-terms in OFFTK	MS – Importance of cross-terms will be related to a number of types			Not started
Charges
GCN charge model	high				In a few steps: conda-installable tool to assign charges integration of tool into OFFTK under ChargeIncrementModel keyword (and exposure of relevant keywords)			in progress	@John Chodera @Yuanqing Wang @Josh Fass (Deactivated) (maybe John Herr)
Off-site charge SMIRKS definition/fitting/benchmarking	medium	high		VirtualSite support in OFFTK	Helpful discussion in Slack: https://openforcefieldgroup.slack.com/archives/C1907SGET/p1590251452068100 Infrastructure expected in September 2020			Not started	spinoff (but interface with @David Cerutti (Deactivated) work?)
Bayesian inference and surrogate modeling
Testing Bayesian inference on an analytical model	medium	Low			Nearing completion			in progress	@Owen Madin
Generalizing analytical model for Bayesian inference and testing methods	LOW	medium			Proof-of-concept work to give us an analytical form for early testing			in progressslower	@Owen Madin (and a student)
Constructing full Bayesian architecture with reweighting and simulation to build surrogate models	LOW	high	Analytical Bayesian inference testing		ForceBalance → pytorch, torchMD (timemachine)			Not started	John Herr @Owen Madin (science, not software)
Automated typing inference from scratch	high	high			Bayesian-based typing (Josh Fass’s work)				@Josh Fass (Deactivated) → @Tobias Huefner
Other
Water co-optimization planning study (to be executed later) – discuss with @Lee-Ping Wang	Low	high			Lack of bandwidth, potentially Bill Swope could help advise with data selection.				spinoff
Thinking about metals / ions / salts	Low	high			Biologically relevant, will become high priority at some point				spinoff
Thinking about ionic liquids
Alchemical force fields (for alchemical free energies)	Low/MEDIum				Soft core potentials. JDC might have people in his lab working on it, MS is interested to join the effort.
Continuous (smearnoff) typing					ESPALOMA				@Yuanqing Wang