title: Coarse-Grained Prediction of Peptide Binding to G-Protein Coupled Receptors.
abstract: In 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, NTS8-13and 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.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.
authors.forename: Bartholomé
authors.initials: B
authors.lastname: Delort
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.|Centre de Biochimie Structurale (CBS), UMR5048, CNRS, Université de Montpellier , INSERM U1054, 29 rue de Navacelles, 34090 Montpellier, France.
authors.forename: Pedro
authors.initials: P
authors.lastname: Renault
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.
authors.forename: Landry
authors.initials: L
authors.lastname: Charlier
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Raussin
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.
authors.forename: Jean
authors.identifier: 0000-0002-4551-4254
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier, Faculté de Pharmacie , 15 Avenue Charles Flahault, BP 14491, 34093 Montpellier, Cedex 05, France.
authors.forename: Nicolas
authors.identifier: 0000-0002-3883-2852
authors.initials: N
authors.lastname: Floquet
mesh_terms: D004220:Disulfides / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009496:Neurotensin / Q000737:chemistry / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D019718:Receptors, CXCR4 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004220:Disulfides; D010456:Peptides, Cyclic; D019718:Receptors, CXCR4; D009496:Neurotensin