Open Free Energy
@openfree.energy
Pinned
Large-scale collaborative assessment of binding free energy calculations for drug discovery using OpenFE
Accurately measuring compound binding affinities is key to driving the pharmaceutical development process. Rigorous physics-based in silico approaches, particularly alchemical free energy methods, hav...
chemrxiv.org
OpenFE is ready for production! chemrxiv.org/engage/chemr...
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
Reposted by Open Free Energy
In October of 2025 we released alchemiscale v0.7.0, and followed this up with v0.7.1 and v0.7.2. We wanted to take a moment to highlight these releases, and the improvements they bring for @openfree.energy users!
alchemiscale.org/advancements...
#compchem #opensource #alchemistry #openscience
alchemiscale.org/advancements...
#compchem #opensource #alchemistry #openscience
advancements in alchemiscale v0.7
In October of this year we released alchemiscale v0.
alchemiscale.org
January 14, 2026 at 7:45 PM
In October of 2025 we released alchemiscale v0.7.0, and followed this up with v0.7.1 and v0.7.2. We wanted to take a moment to highlight these releases, and the improvements they bring for @openfree.energy users!
alchemiscale.org/advancements...
#compchem #opensource #alchemistry #openscience
alchemiscale.org/advancements...
#compchem #opensource #alchemistry #openscience
Reposted by Open Free Energy
OpenBind is a new open science effort to dramatically increase the number of protein:ligand structures in the PDB, pairing this with high-quality affinity data to enable a new generation of predictive structure and affinity models for drug discovery. Check it out: openbind.ai
January 12, 2026 at 2:54 PM
OpenBind is a new open science effort to dramatically increase the number of protein:ligand structures in the PDB, pairing this with high-quality affinity data to enable a new generation of predictive structure and affinity models for drug discovery. Check it out: openbind.ai
Reposted by Open Free Energy
Exciting news! We have a new website: omsf.io/alchemistry
Your one-stop shop for everything related to our conference community. 🎉
BTW, registration is now open, so head over to secure your spot! We'll be sharing updates and details about the event.
Bookmark it as there's plenty more to come!
Your one-stop shop for everything related to our conference community. 🎉
BTW, registration is now open, so head over to secure your spot! We'll be sharing updates and details about the event.
Bookmark it as there's plenty more to come!
Alchemistry Workshop in Free Energy Methods for Drug Design - Alchemistry
Annual conference on Free Energy Methods in Drug Discovery
omsf.io
January 5, 2026 at 8:33 PM
Exciting news! We have a new website: omsf.io/alchemistry
Your one-stop shop for everything related to our conference community. 🎉
BTW, registration is now open, so head over to secure your spot! We'll be sharing updates and details about the event.
Bookmark it as there's plenty more to come!
Your one-stop shop for everything related to our conference community. 🎉
BTW, registration is now open, so head over to secure your spot! We'll be sharing updates and details about the event.
Bookmark it as there's plenty more to come!
To our knowledge, this is the first study to report binding free energy benchmarks on a cross-company collection of proprietary datasets. We couldn't have done it without the hard work of our amazing partner companies!
December 18, 2025 at 7:18 PM
To our knowledge, this is the first study to report binding free energy benchmarks on a cross-company collection of proprietary datasets. We couldn't have done it without the hard work of our amazing partner companies!
Across a total of 1,700 ligands, OpenFE shows robust performance, generates reproducible results, and achieves both sufficient throughput and rapid convergence.
Our protocol:
- ranks compounds about as well as commercial solutions
- does not require fine-tuning settings for each system
Our protocol:
- ranks compounds about as well as commercial solutions
- does not require fine-tuning settings for each system
December 18, 2025 at 7:17 PM
Across a total of 1,700 ligands, OpenFE shows robust performance, generates reproducible results, and achieves both sufficient throughput and rapid convergence.
Our protocol:
- ranks compounds about as well as commercial solutions
- does not require fine-tuning settings for each system
Our protocol:
- ranks compounds about as well as commercial solutions
- does not require fine-tuning settings for each system
OpenFE is ready for production! chemrxiv.org/engage/chemr...
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
Large-scale collaborative assessment of binding free energy calculations for drug discovery using OpenFE
Accurately measuring compound binding affinities is key to driving the pharmaceutical development process. Rigorous physics-based in silico approaches, particularly alchemical free energy methods, hav...
chemrxiv.org
December 18, 2025 at 7:12 PM
OpenFE is ready for production! chemrxiv.org/engage/chemr...
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
In collaboration with our industry partners, we ran benchmarking simulations of our hybrid-topology RBFE protocol on a large collection of both public and private protein-ligand binding datasets.
#compchem
Reposted by Open Free Energy
Jeff Wagner and Jen Clark ran a workshop at the @mdanalysis.bsky.social UGM in Arizona last week, in coordination with the @openfree.energy team.
November 17, 2025 at 4:43 PM
Jeff Wagner and Jen Clark ran a workshop at the @mdanalysis.bsky.social UGM in Arizona last week, in coordination with the @openfree.energy team.
Our docs have you covered! We have a "cookbook" demonstrating how to use our API for a variety of tasks in setting up free energy calculations. docs.openfree.energy/en/latest/co...
Cookbook — OpenFE documentation
docs.openfree.energy
November 11, 2025 at 2:55 PM
Our docs have you covered! We have a "cookbook" demonstrating how to use our API for a variety of tasks in setting up free energy calculations. docs.openfree.energy/en/latest/co...
Our command line interface (CLI) is designed to provide easy access to our tested, production-ready workflow. But if you are developing new methods or pioneering workflows, you may need the power and flexibility of our application programming interface (API) in #Python. #compchem
November 11, 2025 at 2:55 PM
We've just released openfe v1.7, which includes includes new protocols for Separated Topologies and Absolute Binding Free Energies, as well as up to 2x faster simulations using the default settings.
openfree.energy/science/upda...
openfree.energy/science/upda...
openfe v1.7.0: SepTop, ABFEs, faster simulations, and more!
We are pleased to announce the release of openfe version 1.7.0!
openfree.energy
October 24, 2025 at 5:20 PM
We've just released openfe v1.7, which includes includes new protocols for Separated Topologies and Absolute Binding Free Energies, as well as up to 2x faster simulations using the default settings.
openfree.energy/science/upda...
openfree.energy/science/upda...
We tested Sage 2.3.0rc2 from @openforcefield.org in RBFE benchmarks and found it improves accuracy on some of our benchmark systems like p38. Can't wait to see the GNN charge model become default!
October 14, 2025 at 5:41 PM
We tested Sage 2.3.0rc2 from @openforcefield.org in RBFE benchmarks and found it improves accuracy on some of our benchmark systems like p38. Can't wait to see the GNN charge model become default!
Reposted by Open Free Energy
We’re pleased to announce Sage 2.3.0 Release Candidate 2 (rc2)! Sage 2.3.0 will be the first OpenFF force field to use the AshGC neural network charge model, which was trained to AM1BCC ELF10 charges, and allows for rapid charge assignment for molecules with hundreds or thousands of heavy atoms.
October 10, 2025 at 3:02 PM
We’re pleased to announce Sage 2.3.0 Release Candidate 2 (rc2)! Sage 2.3.0 will be the first OpenFF force field to use the AshGC neural network charge model, which was trained to AM1BCC ELF10 charges, and allows for rapid charge assignment for molecules with hundreds or thousands of heavy atoms.
Reposted by Open Free Energy
Save the date, my fellow computational alchemists! The upcoming '26 Workshop on Free Energy Methods in Drug Design will be held in Barcelona, Spain, on May 4-6, 2026. The registration link will be sent soon!
September 23, 2025 at 5:36 PM
Save the date, my fellow computational alchemists! The upcoming '26 Workshop on Free Energy Methods in Drug Design will be held in Barcelona, Spain, on May 4-6, 2026. The registration link will be sent soon!
OpenFE is being used to predict affinity of molecular glues!
Check out the new preprint from the team at Ternary Therapeutics: chemrxiv.org/engage/chemr...
Check out the new preprint from the team at Ternary Therapeutics: chemrxiv.org/engage/chemr...
Optimizing Molecular Glues Using Free Energy Perturbation and Cofolding Methods
Molecular glues, a class of small molecules that induce protein-protein interactions, hold significant promise as a therapeutic modality, offering access to new biology unlocking new protein targets w...
chemrxiv.org
September 11, 2025 at 2:53 PM
OpenFE is being used to predict affinity of molecular glues!
Check out the new preprint from the team at Ternary Therapeutics: chemrxiv.org/engage/chemr...
Check out the new preprint from the team at Ternary Therapeutics: chemrxiv.org/engage/chemr...
You can find more information starting on slide 20 in our February 2025 update presentation: zenodo.org/records/1486...
zenodo.org
August 27, 2025 at 7:28 PM
You can find more information starting on slide 20 in our February 2025 update presentation: zenodo.org/records/1486...
To address these challenging cases, the Open Force Field Intitiative provides a tool, “BespokeFit,” for generating custom parameters for the specific chemistry of a target molecule. These custom (or “bespoke”) parameters can be used in RBFE calculations in OpenFE.
August 27, 2025 at 7:27 PM
To address these challenging cases, the Open Force Field Intitiative provides a tool, “BespokeFit,” for generating custom parameters for the specific chemistry of a target molecule. These custom (or “bespoke”) parameters can be used in RBFE calculations in OpenFE.
Our default force field, OpenFF “Sage,” works well on a wide variety of organic molecules relevant to drug design. However, projects involving more exotic functional groups may be limited by low force field accuracy.
August 27, 2025 at 7:26 PM
Our default force field, OpenFF “Sage,” works well on a wide variety of organic molecules relevant to drug design. However, projects involving more exotic functional groups may be limited by low force field accuracy.
Did you know you can use custom force field parameters in OpenFE? Try out this cookbook to learn more! docs.openfree.energy/en/latest/co... #compchem
BespokeFit: Using bespoke force field parameters with OpenFE protocols — OpenFE documentation
docs.openfree.energy
August 27, 2025 at 7:25 PM
Did you know you can use custom force field parameters in OpenFE? Try out this cookbook to learn more! docs.openfree.energy/en/latest/co... #compchem
This is such cool work. Ivan from the Chodera Lab is implementing a protein mutation protocol in OpenFE, and we can't wait to see what incredible studies people do with it!
August 19, 2025 at 5:05 PM
This is such cool work. Ivan from the Chodera Lab is implementing a protein mutation protocol in OpenFE, and we can't wait to see what incredible studies people do with it!
It's great to see this work in print! It's not on our roadmap this year, but in the longer term we are interested in optimizing replica spacing and will look closely at your method.
June 24, 2025 at 1:16 AM
It's great to see this work in print! It's not on our roadmap this year, but in the longer term we are interested in optimizing replica spacing and will look closely at your method.
But the ability of Boltz-2 to predict affinity opens up new possibilities for drug design workflows, like the Affinity Funneling approach that David Pearlman describes here.
medium.com/@dapscience/...
medium.com/@dapscience/...
Boltz-2 vs. FEP? The Wrong Question. Here’s Why They’re Stronger Together
The Boltz-2 AI model lays claim to some amazing improvements in ligand affinity prediction. The greatest value may be in the realms of…
medium.com
June 17, 2025 at 4:00 PM
But the ability of Boltz-2 to predict affinity opens up new possibilities for drug design workflows, like the Affinity Funneling approach that David Pearlman describes here.
medium.com/@dapscience/...
medium.com/@dapscience/...
Alchemical free energy simulations will remain a crucial step in teh drug design process for their accuracy and reliability, especially in binding pockets that rearrange to accommodate different ligands.
www.deepmirror.ai/post/boltz-2...
#opensource #compchem #boltz2
www.deepmirror.ai/post/boltz-2...
#opensource #compchem #boltz2
Evaluating Boltz-2 on Real Drug Targets: Does it work? | deepmirror
Evaluating Boltz-2 on Real Drug Targets: Does it work?
www.deepmirror.ai
June 17, 2025 at 3:59 PM
Alchemical free energy simulations will remain a crucial step in teh drug design process for their accuracy and reliability, especially in binding pockets that rearrange to accommodate different ligands.
www.deepmirror.ai/post/boltz-2...
#opensource #compchem #boltz2
www.deepmirror.ai/post/boltz-2...
#opensource #compchem #boltz2
It's exciting to see our software used as a benchmark for cutting-edge AI methods!
On the standard FEP+ affinity benchmark, whose targets were held out of training, Boltz-2 achieves an average Pearson of 0.62—comparable to OpenFE, a widely adopted open-source FEP pipeline, while being over 1000x faster!
June 13, 2025 at 1:01 AM
It's exciting to see our software used as a benchmark for cutting-edge AI methods!
Reposted by Open Free Energy
This poster illustrates the substantial flexibility of the open source @openfree.energy ecosystem, enabling unconventional approaches for applying free energy methods. As this ecosystem continues to evolve, I'm excited to see what users do with the advancements we make!
May 27, 2025 at 11:27 PM
This poster illustrates the substantial flexibility of the open source @openfree.energy ecosystem, enabling unconventional approaches for applying free energy methods. As this ecosystem continues to evolve, I'm excited to see what users do with the advancements we make!
If you weren't at @feworkshop.bsky.social in Boston last week, you missed Hannah Baumann giving the first sneak peek at results from our partner benchmarking study! Fortunately for you, Josh Horton wrote up a blog post about the early results: blog.omsf.io/the-free-ene...
#compChem
#compChem
The Free Energy of Everything: Benchmarking OpenFE
Written by: Josh Horton, PhD
Who is OpenFE and what do they do?
Open Free Energy (OpenFE) sits at the nexus of academia and industry. We are developing an open-source software ecosystem for alchem...
blog.omsf.io
May 15, 2025 at 2:00 PM
If you weren't at @feworkshop.bsky.social in Boston last week, you missed Hannah Baumann giving the first sneak peek at results from our partner benchmarking study! Fortunately for you, Josh Horton wrote up a blog post about the early results: blog.omsf.io/the-free-ene...
#compChem
#compChem