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Updated: May 17, 2026

Protein Target Prediction and Validation of Small Molecule Compound
Published on: February 23, 2024
How good are state-of-the-art docking tools in predicting ligand binding modes in protein-protein interfaces?
Dennis M Krüger1, Gisela Jessen, Holger Gohlke
1Institute of Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University, Universitätsstr.1, 40225 Düsseldorf, Germany.
Abstract:
Protein-protein interfaces (PPIs) are an important class of drug targets. We report on the first large-scale validation study on docking into PPIs. DrugScore-adapted AutoDock3 and Glide showed good success rates with a moderate drop-off compared to docking to "classical targets". An analysis of the binding energetics in a PPI allows identifying those interfaces that are amenable for docking. The results are important for deciding if structure-based design approaches can be applied to a particular PPI.
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