README.md

Benchmark sets for free energy calculations

This repository relates to the perpetual review (definition) paper called "Predicting binding free energies: Frontiers and benchmarks" by David L. Mobley, Germano Heinzelmann, Niel M. Henriksen, and Michael K. Gilson. The repository's focus is benchmark sets for binding free energy calculations, including the perpetual review paper, but also supporting files and other materials relating to free energy benchmarks. Thus, the repository includes not only the perpetual review paper but also further discussion, datasets, and (hopefully ultimately) standards for datasets and data deposition.

The latest version of the paper is always available on this GitHub repository, as well as all previous versions. Additionally, all release versions -- current and prior -- are available via Zenodo DOIs, with the latest release at this DOI:

The paper

Versions

The most up-to-date version of our perpetual review paper always available here. Additionally, this repository provides the authoritative source for all versions of this paper. Released versions of the paper are also archived as preprints on eScholarship, and have Zenodo DOIs as noted above. An early version of this work was published in Annual Review of Biophysics 46:531-558 (2017).

Publication in Annual Review

While a portion of this work was originally published with Annual Review, the version here is substantially expanded and updated, and will continue to deviate further from the AR version. Thus, we refer to this version as the "perpetual review version" and this is refelected in its title.

Ongoing updates and credit

Source files for the paper are deposited here on this GitHub repository, as detailed below, and comments/suggestions, etc. are welcome via the issue tracker (https://github.com/MobleyLab/benchmarksets/issues).

The Annual Review portion of this work is posted with permission from the Annual Review of Biophysics, Volume 46 © 2017 by Annual Reviews. Only the Annual Reviews version of the work is peer reviewed; versions posted here are effectively preprints updated at the authors' discretion. The right to create derivative works (exercised here) is also exercised with permission from the Annual Review of Biophysics, Volume 46 © 2017 by Annual Reviews, http://www.annualreviews.org/

A list of authors is provided below.

Citing this work

To cite this work, please cite both:

• The latest eScholarship version (archiving point releases of this repo) at https://escholarship.org/uc/item/9p37m6bq, with the authors currently listed there and the title "Predicting binding free energies: Frontiers and benchmarks (a perpetual review)"
• Our Annual Review in Biophysics work (DOI)

The vision

The field vitally needs benchmark sets to test and advance free energy calculations, as we detail in our paper. Currently, there are no such standard benchmark systems. And when good test systems are found, the relevant data tends to be published but then forgotten, and never becomes widely available. Here, we want the community to be involved in selecting benchmark systems, highlighting their key challenges, and making the data and results readily available to drive new science.

To make this happen, we need community input. Please bring new, relevant work to our attention, including experimental or modeling work on the benchmark systems currently available here, or new work on systems that might make good candidate benchmark systems for the future. And please help us create consensus around a modest set of benchmark systems which can be used to drive forward progress in the field.

The benchmark sets

Currently proposed benchmark sets are detailed in the paper and include:

• Host guest systems
  • CB7
  • Gibb deep cavity cavitands (GDCCs) OA and TEMOA
  • Cyclodextrins (alpha and beta)
• Lysozyme model binding sites
  • apolar L99A
  • polar L99A/M102Q
• Bromodomain BRD4-1

Other near-term candidates include:

• Thrombin
• Suggest and vote on your favorites via a feature request below

Community involvement is needed to pick and advance the best benchmarks.

Get involved

We need your help to pick the most informative systems, identify the challenges they present, and help make them standard benchmarks. Please provide your input:

Vote on what we should do next

For long-term directions, please help us prioritize what we ought to be doing in terms of benchmarks and other changes. Please click below to vote on one of these priorities or to suggest your own (such as addition of specific benchmark systems):

Submit an issue

If you have a specific suggestion or request relating to the material on GitHub or our paper, please submit a request on our issue tracker.

Submit a pull request

We also welcome contributions to the material which is already here to extend it (see Section IV in our paper) and encourage you to actually propose changes via a "pull request", even to the paper itself. This will allow us to track your contributions, as well. Specifically, the full list of contributors to the updated paper and data can be appended to subsequent versions of this work, as they would be for a software project. New versions of this work are assigned unique, cite-able DOIs and essentially constitute preprints, so they can be cited as interim research products.

Authors

• David L. Mobley (UCI)
• Germano Heinzelmann (Universidade Federal de Santa Catarina)
• Niel M. Henriksen (UCSD)
• Michael K. Gilson (UCSD)

Your name, too, can go here if you help us substantially revise/extend the paper.

Acknowledgments

We want to thank the following people who contributed to this repository and the paper, in addition to those acknowledged within the text itself

• David Slochower (UCSD, Gilson lab): Grammar corrections and improved table formatting
• Nascimento (in a comment on biorxiv): Highlighted PDB code error for n-phenylglycinonitrile
• Jian Yin (UCSD, Gilson lab): Provided host-guest structures and input files for the CB7 and GDCC host-guest sets described in the paper

Please note that GitHub's automatic "contributors" list does not provide a full accounting of everyone contributing to this work, as some contributions have been received by e-mail or other mechanisms.

Versions

• AR: Annual Review in Biophysics 46:531-558 (2017). This version split from this repo around the time of the 1.0 release below.
• v1.0: As posted to bioRxiv
• v1.0.1 (10.5281/zenodo.155330): Incorporating improved tables and typo fixes from D. Slochower; also, versions now have unique DOIs via Zenodo.
• v1.0.4 (10.5281/zenodo.167349): Maintenance version fixing an incorrect PDB code and adding a new reference and some new links.
• v1.1 (10.5281/zenodo.197428): Adds significant additional discussion on potential future benchmark sets, needs for workflow science, etc. See release notes for more details. Versions also now include the date and version number within the PDF.
• v1.1.1 (10.5281/zenodo.254619): Adds input files for host-guest benchmarks; some revisions to text as recommended by Annual Reviews. See release notes for more details.
• v1.1.2 (10.5281/zenodo.569575): Adds consistently handled SMILES for aromatics, Annual Reviews copyright/rights info in TeX and README, additional citation information for one reference, and new discussion of some new bromodomain absolute binding free energy work.
• v1.1.3 (10.5281/zenodo.571227): Changes title to include "(a perpetual review)" to make more clear that this is not the same paper as the Annual Reviews version; makes clarifications to README.md about which version is which.
• v1.1.4 (10.5281/zenodo.838361): Updates README.md to reflect publication; clarify differences in material; reflect availability on eScholarship. Updates paper to reflect migration to eScholarship rather than bioRxiv.
• v1.2 (10.5281/zenodo.839047): Addition of bromodomain BRD4(1) test cases as a new ``soft'' benchmark, with help from Germano Heinzelmann. Addition of Heinzelmann as an author. Addition of files for BRD4(1) benchmark. Removed bromodomain material from future benchmarks in view of its presence now as a benchmark system.
• v1.3: Include cyclodextrin benchmarks to data and to paper; removal of most of cyclodextrin material from future benchmarks. Addition of Niel Henriksen as an author based on his work on this. BRD4(1) changes: Reorganize data files; improve BRD4(1) README; switch sd to sdf files; give each BRD4(1) ligand a unique identifier specific to this paper.

Changes not yet in a release

• Add info on how to cite this paper to main README.md
• Fix experimental reference for catechol binding free energy value in Table VIII

Manifest

• paper: Provides LaTeX source files and final PDF for the current version of the manuscript (reformatted and expanded from the version submitted to Ann. Rev. and with 2D structures added to the tables); images, etc. are also available in sub-directories, as is the supporting information.
• input_files: Ultimately to include structures and simulation input files for all of the benchmark systems present as well as (we hope) gold standard calculated values for these files. Currently this includes:
  • README.md: A more extensive document describing the files present
  • BRD4 structures and simulation input files from Germano Heinzelmann
  • CB7 structures and simulation input files from Jian Yin (Gilson lab)
  • GDCC structures and simulation input files from Jian Yin (Gilson lab)
  • Cyclodextrin structures and simulation input files from Niel Henriksen (Gilson lab)