Performance of Protein–Ligand Docking with Simulated Chemical Shift Perturbations

Protein chemical shift perturbations (CSPs) that result from the binding of a ligand to the protein contain structural information about the complex. Therefore, the CSP data, typically obtained during library screening from two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, are often available before attempts to solve the experimental structure of the complex are started, and can be used to solve the complex structure with CSP-based docking. Here, we compare the performance of the post-docking filter and the guided-docking approaches using either amide or α-proton CSPs with 10 protein–ligand complexes. We show that the comparison of experimental CSPs with CSPs simulated for virtual ligand positions can be used to evidence protein conformational change upon binding and possibly improve the CSP-based docking.