PepCrawler: A Fast RRT-Like Algorithm for High-Resolution Refinement and Binding-Affinity Estimation of Peptide Inhibitors

摘要

Design of protein-protein interaction (PPI) inhibitors is a key challenge in Structural Bioinformatics and Computer Aided Drug Design [1, 2]. Peptides, which partially mimic the interface area of one of the interacting proteins, are natural candidates to form protein-peptide complexes competing with the original PPI [3, 4]. Some inhibitory peptides were designed by deriving a short linear segment from one of the proteins in a given PPI complex [5-9]. These peptides were successfully able to inhibit interactions with the partner protein. The prediction of such complexes is especially challenging due to the high flexibility of peptide conformations.