Docking small peptides remains a great challenge: An assessment using AutoDock Vina

Abstract

There is a growing interest in themechanisms and the prediction of how flexible peptides bind proteins, often in a highly selective and conservedmanner. While both existing small-molecule dockingmethods and customprotocols can be used, even short peptidesmake difficult targets owing to their high torsional flexibility. Any benchmarking should therefore start with those. We compiled a meta-data set of 47 complexes with peptides up to five residues, based on 11 related studies fromthe past decade. Although their highly varying strategies and constraints preclude direct, quantitative comparisons, we still provide a comprehensive overview of the reported results, using a simple yet stringentmeasure: the quality of the top-scoring peptide pose. Using the entire data set, this is augmented by our own benchmark of AutoDock Vina, a freely available, fast and widely used docking tool. It particularly addresses non-expert users and was therefore implemented in a highly integratedmanner. Guidelines addressing important issues such as the amount of sampling required for result re- producibility are so far lacking. Using peptide docking as an example, this is the first study to address these issues in detail. Finally, to encourage further, standardized benchmarking efforts, the compiled data set is made available in an accessible, transparent and extendablemanner.