title: FEW: a workflow tool for free energy calculations of ligand binding.
abstract: 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.
authors.affiliation: Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Homeyer
authors.forename: Holger
authors.initials: H
authors.lastname: Gohlke
mesh_terms: D000465:Algorithms; D000925:Anticoagulants / Q000737:chemistry*; D015195:Drug Design; D015951:Factor Xa / Q000737:chemistry*; D065427:Factor Xa Inhibitors; D006801:Humans; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012984:Software; D013816:Thermodynamics
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D008024:Ligands; D015951:Factor Xa