Free Energy and MD Toolkit using OpenMM

A comprehensive toolkit for predicting free energies

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The femto framework aims to offer not only a compact and comprehensive toolkit for predicting binding free energies using methods including ATM and SepTop, but also a full suite of utilities for running advanced simulations using OpenMM, including support for HREMD and REST2.

Warning

From version 0.3.0 onwards, the codebase was re-written to completely remove the dependency on parmed, allowing easy use of any force field parameters in OpenFF, Amber, and OpenMM FFXML formats. This re-write also introduced a number of neccessary API changes. See the migration guide for more details.

Further, the default protocols selected for the ATM and SepTop methods are still being tested and optimized, and may not be optimal. It is recommended that you run a few test calculations to ensure that the results are reasonable.

Installation

This package can be installed using conda (or mamba, a faster version of conda):

mamba install -c conda-forge femto

If you are running with MPI on an HPC cluster, you may need to instruct conda to use your local installation depending on your setup

mamba install -c conda-forge femto "openmpi=4.1.5=*external*"

where in this example you should change 4.1.5 to match the version of OpenMPI installed on your cluster / machine.

Getting Started

To get started, see the usage guide.

Acknowledgements

This framework benefited hugely from the work of Psivant's Open Science Fellows.

ATM

The ATM implementation is based upon the work and advice of E. Gallicchio et al:

• Wu, Joe Z., et al. "Alchemical transfer approach to absolute binding free energy estimation." Journal of Chemical Theory and Computation 17.6 (2021): 3309-3319.
• Azimi, Solmaz, et al. "Relative binding free energy calculations for ligands with diverse scaffolds with the alchemical transfer method." Journal of Chemical Information and Modeling 62.2 (2022): 309-323.

SepTop

The SepTop implementation is based upon the work and advice of H. M. Baumann, D. L. Mobley et al:

• Rocklin, Gabriel J., David L. Mobley, and Ken A. Dill. "Separated topologies—A method for relative binding free energy calculations using orientational restraints." The Journal of chemical physics 138.8 (2013).
• Baumann, Hannah M., et al. "Broadening the scope of binding free energy calculations using a Separated Topologies approach." Journal of Chemical Theory and Computation 19.15 (2023): 5058-5076.