Assessment of Binding Affinity via Alchemical Free-Energy Calculations
Citations Over TimeTop 1% of 2020 papers
Abstract
Free-energy calculations have seen increased usage in structure-based drug design. Despite the rising interest, automation of the complex calculations and subsequent analysis of their results are still hampered by the restricted choice of available tools. In this work, an application for automated setup and processing of free-energy calculations is presented. Several sanity checks for assessing the reliability of the calculations were implemented, constituting a distinct advantage over existing open-source tools. The underlying workflow is built on top of the software Sire, SOMD, BioSimSpace, and OpenMM and uses the AMBER 14SB and GAFF2.1 force fields. It was validated on two datasets originally composed by Schrödinger, consisting of 14 protein structures and 220 ligands. Predicted binding affinities were in good agreement with experimental values. For the larger dataset, the average correlation coefficient Rp was 0.70 ± 0.05 and average Kendall's τ was 0.53 ± 0.05, which are broadly comparable to or better than previously reported results using other methods.
Related Papers
- → Workflow Reuse in Practice: A Study of Neuroimaging Pipeline Users(2014)15 cited
- A Workflow Event Logging Mechanism and Its Implications on Quality of Workflows(2010)
- Workflow Analysis using Graph Kernels.(2010)
- → Utilizing Tags for Scientific Workflow Recommendation(2019)2 cited
- Configurable and Collaborative Scientific Workflows(2014)