Department of Pharmaceutical Sciences, UCI

This is a talk/status report given on our BLUES technique for estimating fragment binding mode occupancies; it was presented at the OpenEye CUP Meeting in Santa Fe, NM, March 8, 2018. This work is in the area of structure-based drug design and we are working on modeling techniques to efficiently estimate populations of metastable ligand binding modes. The presentation is made available in PowerPoint and Keynote formats and includes movies, so the files are large.

This provides access to the late J. Peter Guthrie's small molecule hydration free energy database, which was donated posthumously to the community. This is an archival copy of material also maintained on GitHub at https://github.com/mobleylab/GuthrieSolv. If you are interested in using the data provided here, please read the relevant background information and disclaimers provided in the included README.md file, and consider contributing to curation of the dataset.

Binding free energy calculations based on molecular simulations provide predicted affinities for biomolecular complexes.These calculations begin with a detailed description of a system, including its chemical composition and the interactions between its components.Simulations of the system are then used to compute thermodynamic information, such as binding affinities.Because of their growing promise for guiding molecular design, these calculations have recently begun to see widespread applications in early stage drug discovery.However, many challenges remain to make them a robust and reliable tool. Here, we highlight key challenges facing these calculations, describe known examples of these challenges, and call for the designation of standard community benchmark test systems that will help the research community generate and evaluate progress.In our view, progress will require careful assessment and evaluation of new methods, force fields, and modeling innovations on well-characterized benchmark systems, and we lay out our vision for how this can be achieved.

   This repository relates to the perpetual review (definition) paper called "Predicting binding free energies: Frontiers and benchmarks" by David L. Mobley, Germano Heinzelmann and Michael K. Gilson. Its focus is benchmark sets for binding free energy calculations, including the perpetual review paper, but also all things relating to benchmark sets for free energy calculations. This includes discussion, datasets, and standards for datasets and data deposition.

   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/

   Updated versions of this work are maintained at github.com/mobleylab/benchmarksets and this eScholarship archive serves to archive release versions of the work.

This provides input files, results, and raw energy data associated with the v0.5 update of the FreeSolv database of hydration free energies.

This provides electronic supporting materials, especially input files and trajectory files, associated with our work "Is ring breaking feasible in relative binding free energy calculations?" 

This work provides a curated database of experimental and calculated hydration free energies for small molecules in water, along with experimental values and input files. Experimental values are taken from prior literature and will continue to be curated, with updated experimental references and data added as it becomes available. Calculated values are based on the GAFF small molecule force field in TIP3P water with AM1-BCC charges, as in the provided parameter files. Values were calculated using the GROMACS simulation package, with full details given in references cited within the database itself. This database builds on previous work from the Mobley lab and others, and extends the prior database. With deposition in eScholarship, the database is now versioned, allowing citation of specific versions of the database, and easier updates.  

A change log is provided in the PDF file associated with each version.

Latest version, v0.32, Sept. 29, 2015.