title: Molecular recognition in chemical and biological systems.
abstract: Structure-based ligand design in medicinal chemistry and crop protection relies on the identification and quantification of weak noncovalent interactions and understanding the role of water. Small-molecule and protein structural database searches are important tools to retrieve existing knowledge. Thermodynamic profiling, combined with X-ray structural and computational studies, is the key to elucidate the energetics of the replacement of water by ligands. Biological receptor sites vary greatly in shape, conformational dynamics, and polarity, and require different ligand-design strategies, as shown for various case studies. Interactions between dipoles have become a central theme of molecular recognition. Orthogonal interactions, halogen bonding, and amide⋅⋅⋅π stacking provide new tools for innovative lead optimization. The combination of synthetic models and biological complexation studies is required to gather reliable information on weak noncovalent interactions and the role of water.
authors: Laboratorium für Organische Chemie, Departement Chemie und Angewandte Biowissenschaften, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich (Switzerland).
authors: Elke
authors: E
authors: Persch
authors: Oliver
authors: O
authors: Dumele
authors: François
authors: F
authors: Diederich
mesh_terms: D001690:Biological Science Disciplines; D002626:Chemistry, Pharmaceutical; D008958:Models, Molecular; D014867:Water / Q000737:chemistry*
chemical_list: D014867:Water
keywords: dipolar interactions; molecular recognition; protein-ligand complexation; supramolecular  chemistry; water