Reduced Dimensionality in Ligand—Protein Structure Prediction: Covalent Inhibitors of Serine Proteases and Design of Site-Directed Combinatorial Libraries
Daniel K. Gehlhaar, Djamal Bouzida, Paul A. Rejto · ACS symposium series · 1999
Structure prediction of ligand-protein complexes is greatly facilitated when the location of ligand functional groups relative to the protein is known. This situation arises in two applications of practical interest: when a covalent bond is formed between the ligand and the protein, and when a fragment of the ligand dominates the molecular recognition with the protein. In both of these cases, it is shown that the predicted structure corresponds to the experimentally observed structure with increased probability. Using this approach, a library of compounds is screened for potential inhibitors of dihydrofolate reductase and porcine pancreatic elastase; known inhibitors were ranked favorably in both cases.