title: Metadynamics Simulations Rationalise the Conformational Effects Induced by N-Methylation of RGD Cyclic Hexapeptides.
abstract: We combined metadynamics, docking and molecular mechanics/generalised born surface area (MM/GBSA) re-scoring methods to investigate the impact of single and multiple N-methylation on a set of RGD cyclopeptides displaying different affinity for integrin αIIbβ3. We rationalised the conformational effects induced by N-methylation and its interplay with receptor affinity, obtaining good agreement with experimental data. This approach can be exploited before entering time-consuming and expensive synthesis and binding experiments.
authors.affiliation: Biomolecular NMR Unit, Ospedale S. Raffaele, Via Olgettina 58, 20132 Milan (Italy).|Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milan (Italy).
authors.forename: Cristina
authors.initials: C
authors.lastname: Paissoni
authors.affiliation: Biomolecular NMR Unit, Ospedale S. Raffaele, Via Olgettina 58, 20132 Milan (Italy). musco.giovanna@hsr.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Ghitti
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milan (Italy).
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.affiliation: Drug Discovery and Development, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa (Italy).
authors.forename: Andrea
authors.initials: A
authors.lastname: Spitaleri
authors.affiliation: Biomolecular NMR Unit, Ospedale S. Raffaele, Via Olgettina 58, 20132 Milan (Italy). ghitti.michela@hsr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Musco
mesh_terms: D001665:Binding Sites; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000378:metabolism; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: docking; integrin; metadynamics; methylation; peptides