Augmenting Structure‐Based Design with Experimental Protein‐Ligand Interaction Data: Molecular Recognition, Interactive Visualization, and Rescoring
| Autor: | Andreas Tosstorff, Richard Bartelt, Bernd Kuhn, Jason C. Cole |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Molecular Structure Drug discovery Computer science Organic Chemistry Stacking Proteins Hydrogen Bonding Ligands Biochemistry Molecular recognition Docking (molecular) Drug Design Drug Discovery Molecular Medicine Relevance (information retrieval) General Pharmacology Toxicology and Pharmaceutics Biological system Lone pair Interactive visualization Protein ligand |
| Zdroj: | ChemMedChem. 16:3428-3438 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.202100387 |
| Popis: | The previously introduced ratio of frequencies (RF ) framework provides statistically sound information on the relative interaction preferences of atoms in crystal structures. By applying the methodology to protein-ligand complexes, we can investigate the significance of interactions that are employed in structure-based drug design. Here, we revisit three aspects of molecular recognition in the light of the RF framework, namely stacking interactions of heteroaromatic rings with protein amide groups, interactions of acidified C-H groups, and interaction differences between syn and anti lone pairs of carboxylate groups. In addition, we introduce a highly interactive visualization tool that facilitates design idea generation in structure-enabled drug discovery projects. Finally, we show that applying the RF analysis as a simple rescoring tool after docking improves enrichment factors for the DUD-E diverse targets subset supporting the relevance of our approach. |
| Databáze: | OpenAIRE |
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