In recent years a large number of novel interaction types have been postulated to have a stabilizing effect on protein-ligand complex formation. However, the significance for some these “unusual” interactions has yet to be validated with experimental and theoretical studies of model systems as well as statistical analyses of crystallographic databases. We have pursued the latter approach and extended the recently published line-of-sight analysis by Taylor to protein-ligand complexes from the Protein Data Bank. With this method confounding secondary interactions are pruned out and statistically significant interaction propensities for different functional groups can be derived. In addition this approach provides insights into the geometric preferences of intermolecular contacts.<br/>As a result of our studies we will present crystal structure based statistical analyses of different interaction types and highlight preferred protein environments of selected functional groups of relevance for medicinal chemistry. This will be complemented by illustrative examples from drug discovery projects.

How significant are unusual intermolecular interactions?

254th National Meeting (2017)

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