ci6b00503_si_006.pdf (222.91 kB)
Coarse-Grained Prediction of Peptide Binding to G‑Protein Coupled Receptors
journal contribution
posted on 2017-02-23, 00:00 authored by Bartholomé Delort, Pedro Renault, Landry Charlier, Florent Raussin, Jean Martinez, Nicolas FloquetIn this study, we
used the Martini Coarse-Grained model with no
applied restraints to predict the binding mode of some peptides to
G-Protein Coupled Receptors (GPCRs). Both the Neurotensin-1 and the
chemokine CXCR4 receptors were used as test cases. Their ligands,
NTS8–13 and CVX15 peptides, respectively, were initially
positioned in the surrounding water box. Using a protocol based on
Replica Exchange Molecular Dynamics (REMD), both opening of the receptors
and entry of the peptides into their dedicated pockets were observed
on the μs time-scale. After clustering, the most statistically
representative orientations were closely related to the X-ray structures
of reference, sharing both RMSD lower than 3 Å and most of the
native contacts. These results demonstrate that such a model, that
does not require access to tremendous computational facilities, can
be helpful in predicting peptide binding to GPCRs as well as some
of the receptor’s conformational changes required for this
key step. We also discuss how such an approach can now help to predict, de novo, the interactions of GPCRs with other intra- or
extracellular peptide/protein partners.