Geometry Optimization Benchmarking for Industry Partners

Driver	Approver	Contributors	Stakeholders

Driver	Approver	Contributors	Stakeholders
@David Dotson @Joshua Horton	@David Hahn	@Trevor Gokey @Jeffrey Wagner	Gary Tresadern, Industry Partners

Objective	Obtain performance benchmarks of OpenFF forcefields via geometry optimizations of in-house molecules by industry partners.
Due date	Jan 31, 2021
Key outcomes	partners can deploy required software with minimal difficulty partners can execute geometry optimizations for the desired list of forcefields on their in-house molecules using their own compute and storage infrastructure geometry optimization results are readily usable to reproduce key figures from the recent benchmarking preprint by Lim et. al.
Status	status:COMPLETE

Problem Statement

The Open Force Field Initiative’s industry partners are keen to benchmark the performance of the recent OpenFF forcefields on their in-house, proprietary molecules. To do so, they will require minimally-complex tooling to perform geometry optimizations on these molecules at reasonable scale (100 to 1000 molecules) using a variety of force fields. They will also require tooling to reproduce key figures from the Lim et. al. preprint for these data.

The results of these calculations will be compiled together for publication.

Scope

Must have:

Each partner should be able to run geometry optimizations on 100 to 1000 proprietary molecules, each with 10 conformers (1,000 - 10,000 optimizations total).
- Molecules that partners are willing to make public will be submitted to the public QCArchive for hosting/compute
The approach cannot be dependent on the OpenEye Toolkit.
Each optimization should be identified by a three-letter company code (COM), molecule-index (XXXXX), conformer-index (YY): COM-XXXXX-YY
Optimizations should be readily usable to reproduce key figures from the Lim et. al. preprint.
The following QM computation specs will be used:
- default
  - program: psi4
  - method: B3LYP-D3BJ
  - basis: DZVP
The following MM force fields shall be used for optimizations with OpenMM:
- smirnoff99Frosst
- openff 1.0.0 1.1.(0,1) 1.2.1 (latest), 1.3.0 (upcoming as of 2020.10.22)
- gaff2.1
Results from calculations must be flat files

Nice to have:

Coverage reporting (how often each parameter used; fragments that could not be parameterized)
- Check if this is a must have
Energy minimizations with Schrodinger using OPLS3e as a separate software path (cannot be done with QC* software stack
- need to obtain consent from Schrodinger for publishing; perhaps a partner can negotiate on behalf of the effort?
Dipole moment-based comparison for optimized geometries
Torsional difference comparison for optimized geometries

Not in scope (for this project; of interest for future projects):

Possibility to run torsion drives
Bespoke parameterization for molecules that can’t be parameterized by existing OpenFF forcefield, followed by benchmarking (requires injection of new parameters into QC* stack; not currently possible)
Benchmarking with MMFF94 and/or cGenFF

Clarifications Needed

What will the input file formats be? Will we enforce 3D SDF for minimal ambiguity?
1. Yes, enforce 3D SDF to remove possibility for ambiguity in inputs

Execution Workflow

Workflow diagram: https://drive.google.com/file/d/1t3zCYj9gYip5FKrvF3Z0GiVdBMHZxmjr/view

Milestones and deadlines

Milestone	Owner	Deadline/Date	Status

Milestone	Owner	Deadline/Date	Status
Meeting with industry partners; gather comprehensive requirements/desires Pharma Partner Benchmark (2020.10.23 slides)	@David Dotson	Oct. 23	status:COMPLETE
Software approach decision settled; ready for execution Benchmarking Software Approach	@David Dotson	Nov. 1	status:COMPLETE
Call for public datasets from industry partners Call for Public Compounds	@Gary Tresadern	Nov. 5	status:COMPLETE
Approach ready for testing by David Hahn, Bill Swope Deployment Procedure Optimization Benchmarking Protocol - Season 1	@David Dotson	Dec. 15	status:COMPLETE
Protocol feature-complete	@David Dotson	Jan. 15	status:COMPLETE
Present protocol to partners	@David Dotson	Jan. 22	status:COMPLETE
Deployment at industry partner sites; protocol burn-in on test set	@David Dotson	Jan. 25	status:COMPLETE
First production runs at industry partner sites initiated	@David Dotson	Feb. 1 Feb. 5	status:COMPLETE
Publicly-sharable exports submission open	@David Dotson	Mar. 23 Apr. 9	status:COMPLETE
Season 1 campaign complete and closed	@David Dotson	Jul. 8	status:COMPLETE

Results

Results can be retrieved from the OpenFF Public Drop Zone.

Force Fields