2007/10/26 by F. Marty Ytreberg, Ytreberg, F. Marty
Biochemistry, Genetics and Molecular Biology · Engineering · Physics and Astronomy · #Biological Physics (physics.bio-ph) #Computational Physics (physics.comp-ph) #Endoplasmic Reticulum Stress and Disease #FOS: Physical sciences #Molecular Junctions and Nanostructures #Protein Structure and Dynamics #physics.bio-ph #physics.comp-ph
paper · pdf · doi:10.48550/arxiv.0710.5132
9 pages, 3 figures (no necessary color). Changes made to methodology and results between revisions
openalex publication_date 2007/10/26 · arxiv created 2008/11/24 · arxiv updated 2009/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
We compute absolute binding affinities for two ligands bound to the FKBP protein using non-equilibrium unbinding simulations. The methodology is straight-forward, requiring little or no modification to many modern molecular simulation packages. The approach makes use of a physical pathway, eliminating the need for complicated alchemical decoupling schemes. Results of this study are promising. For the ligands studied here the binding affinities are typically estimated within less than 4.0 kJ/mol of the target values; and the target values are within less than 1.0 kJ/mol of experiment. These results suggest that non-equilibrium simulation could provide a simple and robust means to estimate protein-ligand binding affinities.