title: Thermodynamically-Weighted Conformational Ensemble of Cyclic RGD Peptidomimetics from NOE Data.
abstract: In the case of flexible molecules, the standard approach of transforming NOE intensities into spatial restraints and of building conformational models minimizing these restraints greatly neglects the richness of molecular conformations. Making use of NOE intensities measured in triplicate and of an iterative molecular-dynamics scheme, we optimized a force field to generate a set of conformations whose ensemble is compatible with the experimental data, and is weighted according to the Boltzmann distribution. This scheme is applied to two cyclic peptidomimetic ligands of integrins. Their difference in binding affinity is recapitulated in terms of their difference in conformational fluctuations.
authors.affiliation: Department of Chemistry, Università degli Studi di Milano , via Golgi 19, 20133 Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Vasile
authors.affiliation: Department of Chemistry, Università degli Studi di Milano , via Golgi 19, 20133 Milano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Civera
authors.affiliation: Department of Chemistry, Università degli Studi di Milano , via Golgi 19, 20133 Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Belvisi
authors.affiliation: Department of Chemistry, Università degli Studi di Milano , via Golgi 19, 20133 Milano, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Potenza
authors.affiliation: Center of Complexity and Biosystems and Department of Physics, Università degli Studi di Milano and INFN , via Celoria 16, 20133 Milano, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Tiana
mesh_terms: D001665:Binding Sites; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry*; D057786:Peptidomimetics / Q000737:chemistry*; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D012910:Snake Venoms / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D008024:Ligands; D010456:Peptides, Cyclic; D057786:Peptidomimetics; D021122:Protein Subunits; D012910:Snake Venoms; C507169:cyclic arginine-glycine-aspartic acid peptide; C422910:Cilengitide