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Structural stability predicts the binding mode of protein-ligand complexes.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Structural stability predicts the binding mode of protein-ligand complexes."

The prediction of a ligand's binding mode into its macromolecular target is essential in structure-based drug discovery. Even though a tremendous effort has been made to address this problem, most of the tools developed work in a similar way, trying to predict the binding free energy associated with each particular binding mode. In this study we decided to abandon this criterium, following structural stability instead. This view, implemented in a novel computational workflow, quantifies the steepness of the local energy minimum associated to each potential binding mode. Surprisingly, the protocol outperforms docking scoring functions in case of fragments (ligands with MW < 300Da) and is as good as docking for drug-like molecules. It also identifies substructures that act as structural anchors, predicting their binding mode with particular accuracy. The results open a new physical perspective for binding mode prediction, which can be combined with existing thermodynamic-based approaches.

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This article was published in the following journal.

Name: Journal of chemical information and modeling
ISSN: 1549-960X
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