A Flexible Docking Procedure for the Exploration of Peptide Binding Selectivity to Known Structures and Homology Models of PDZ Domains

摘要: PDZ domains are important scaffolding modules that typically bind to the C-termini of their interaction partners. Several structures such complexes have been solved, revealing a conserved binding site in domain and an extended conformation bound peptide. A compendium information regarding demonstrates dissimilar C-terminal peptides same domain, different can peptides. detailed understanding PDZ-peptide recognition is needed elucidate this complexity. To end, we designed family docking protocols for (termed PDZ-DocScheme) based on simulated annealing molecular dynamics rotamer optimization, applicable long (20-40 rotatable bonds) both known more complicated problem homology models these domains. The resulting protocol reproduces with 4-8 amino acids within 1-2 from experimental structure when performed original structure. If target apo or model, yields 3 9 out 12 test cases. automated procedure PDZ-DocScheme serve generation structural context validation specificity mutagenesis ligand data.