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

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 seven 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 root-mean-square-deviation measure.

journal_name

Brief Bioinform

authors

Badaczewska-Dawid AE,Kmiecik S,Koliński M

doi

10.1093/bib/bbaa109

subject

Has Abstract

pub_date

2020-06-10 00:00:00

eissn

1467-5463

issn

1477-4054

pii

5855394

pub_type

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