RT Journal Article SR Electronic T1 Predicting binding free energies: Frontiers and benchmarks JF bioRxiv FD Cold Spring Harbor Laboratory SP 074625 DO 10.1101/074625 A1 David L. Mobley A1 Michael K. Gilson YR 2016 UL http://biorxiv.org/content/early/2016/12/08/074625.abstract AB 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 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 briefly explain how the calculations work, highlight key challenges, and argue for the development of accepted benchmark test systems that will help the research community generate and evaluate progress.Manuscript version 1.1.1 pre-release See https://github.com/mobleylab/benchmarksets for all versions.