FEW: a workflow tool for free energy calculations of ligand binding

Journal of Computational Chemistry
Nadine Homeyer, Holger Gohlke


In the later stages of drug design projects, accurately predicting relative binding affinities of chemically similar compounds to a biomolecular target is of utmost importance for making decisions based on the ranking of such compounds. So far, the extensive application of binding free energy approaches has been hampered by the complex and time-consuming setup of such calculations. We introduce the free energy workflow (FEW) tool that facilitates setup and execution of binding free energy calculations with the AMBER suite for multiple ligands. FEW allows performing free energy calculations according to the implicit solvent molecular mechanics (MM-PB(GB)SA), the linear interaction energy, and the thermodynamic integration approaches. We describe the tool's architecture and functionality and demonstrate in a show case study on Factor Xa inhibitors that the time needed for the preparation and analysis of free energy calculations is considerably reduced with FEW compared to a fully manual procedure.


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Related Concepts

Molecular Dynamics
Ligand Binding
Plasma Protein Binding Capacity
Computer Programs and Programming
Indirect Thrombin Inhibitors
Factor Xa Inhibitors [MoA]
Direct Factor Xa Inhibitors

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