Investigating carbohydrate based ligands for galectin-3 with docking and molecular dynamics studies

•Binding free energies of a library of galectin-3 ligands for PET have been calculated.•Docking scores are improved after MD relaxation.•Good agreement between calculated binding energies and available experimental data.•Insights on possible improvement for design of new galectin-3 ligands. Galectin-3 (Gal-3) is a carbohydrate binding protein that is overexpressed in several types of cancers, including pancreatic cancer, which makes it a good target for both imaging and therapeutic drug design. A ligand library specialized for 18F positron emission tomography (PET) has been investigated with molecular dynamics (MD) and free energy methods to determine the relative binding energies of various potential ligands. Our results suggest that traditional docking methods can give good results when complemented by molecular dynamics and free energy methods for these types of ligands. Available experimental binding affinities for a small number of the tested compounds show very good agreement with the calculated energies and provide the rational approach for design of Gal-3 ligands with even higher affinity.