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bioRxiv · 10.1101/2020.03.21.001396

Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement

Badaczewska-Dawid, A.·Kmiecik, S.·Kolinski, M.
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Abstract

The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is important for the discovery of new drugs and deeper understanding of the molecular mechanisms of life. Here we describe a three-stage protocol for the molecular docking of peptides to GPCRs using a set of different programs: (1) CABS-dock for docking fully flexible peptides; (2) PD2 method for the reconstruction of atomistic structures from C-alpha traces provided by CABS-dock and (3) Rosetta FlexPepDock for the refinement of protein-peptide complex structures and model scoring. We evaluated the proposed protocol on the set of 7 different GPCR-peptide complexes (including one containing a cyclic peptide) for which crystallographic structures are available. We show that CABS-dock produces high resolution models in the sets of top-scored models. These sets of models, after reconstruction to all-atom representation, can be further improved by Rosetta high-resolution refinement and/or minimization, leading in most of the cases to sub-Angstrom accuracy in terms of interface RMSD measure.

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Badaczewska-Dawid, A., Kmiecik, S., Kolinski, M.. 2020-03-23. Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement. https://doi.org/10.1101/2020.03.21.001396

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