Parameterization of an effective potential for protein–ligand binding from host–guest affinity data

• DOI: 10.1002/jmr.2489
• Publication Date: 2015-08-10T08:01:44Z
• Authors: Lauren Wickstrom; Nanjie Deng; Peng He; Ahmet Mentes; Crystal Nguyen; Michael K. Gilson; Tom Kurtzman; Emilio Gallicchio; Ronald M. Levy
• Keywords: Binding affinities; Force Field; Affinities

Force field accuracy is still one of the “stalemates” in biomolecular modeling. Model systems with high quality experimental data are valuable instruments for validation and improvement effective potentials. With respect to protein–ligand binding, organic host–guest complexes have long served as models both computational studies because abundance binding affinity available such systems. Binding collected cyclodextrin (CD) inclusion complexes, a popular model molecular recognition, potentially more reliable resource tuning energy parameters than hydration free measurements. Convergence calculations on CD can also be obtained rapidly, thus offering opportunity assess robustness these parameters. In this work, we demonstrate how implicit solvent developed using distribution analysis method (BEDAM) validated Grid Inhomogeneous Solvation Theory analysis. These new solvation were used study two drug targets against HIV‐1 virus improved agreement between calculated affinities. This work illustrates benchmark sets physics‐based evaluate optimize force fields Copyright © 2015 John Wiley & Sons, Ltd.