A protocol for CABS-dock protein–peptide docking driven by side-chain contact information

Abstract

Abstract Background The characterization of protein–peptide interactions is a challenge for computational molecular docking. Protein–peptide docking tools face at least two major difficulties: (1) efficient sampling of large-scale conformational changes induced by binding and (2) selection of the best models from a large set of predicted structures. In this paper, we merge an efficient sampling technique with external information about side-chain contacts to sample and select the best possible models. Methods In this paper we test a new protocol that uses information about side-chain contacts in CABS-dock protein–peptide docking. As shown in our recent studies, CABS-dock enables efficient modeling of large-scale conformational changes without knowledge about the binding site. However, the resulting set of binding sites and poses is in many cases highly diverse and difficult to score. Results As we demonstrate here, information about a single side-chain contact can significantly improve the prediction accuracy. Importantly, the imposed constraints for side-chain contacts are quite soft. Therefore, the developed protocol does not require precise contact information and ensures large-scale peptide flexibility in the broad contact area. Conclusions The demonstrated protocol provides the extension of the CABS-dock method that can be practically used in the structure prediction of protein–peptide complexes guided by the knowledge of the binding interface.

Keywords

• Protein–peptide interactions
• Molecular docking
• Flexible docking
• Protein–peptide complexes