title: On the analysis and comparison of conformer-specific essential dynamics upon ligand binding to a protein.
abstract: The native state of a protein consists of an equilibrium of conformational states on an energy landscape rather than existing as a single static state. The co-existence of conformers with different ligand-affinities in a dynamical equilibrium is the basis for the conformational selection model for ligand binding. In this context, the development of theoretical methods that allow us to analyze not only the structural changes but also changes in the fluctuation patterns between conformers will contribute to elucidate the differential properties acquired upon ligand binding. Molecular dynamics simulations can provide the required information to explore these features. Its use in combination with subsequent essential dynamics analysis allows separating large concerted conformational rearrangements from irrelevant fluctuations. We present a novel procedure to define the size and composition of essential dynamics subspaces associated with ligand-bound and ligand-free conformations. These definitions allow us to compare essential dynamics subspaces between different conformers. Our procedure attempts to emphasize the main similarities and differences between the different essential dynamics in an unbiased way. Essential dynamics subspaces associated to conformational transitions can also be analyzed. As a test case, we study the glutaminase interacting protein (GIP), composed of a single PDZ domain. Both GIP ligand-free state and glutaminase L peptide-bound states are analyzed. Our findings concerning the relative changes in the flexibility pattern upon binding are in good agreement with experimental Nuclear Magnetic Resonance data.
authors.affiliation: Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal, Argentina.
authors.forename: Marcos
authors.initials: M
authors.lastname: Grosso
authors.affiliation: Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal, Argentina.
authors.forename: Adrian
authors.initials: A
authors.lastname: Kalstein
authors.affiliation: Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal, Argentina.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Departments of Physics and Chemistry, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Roitberg
authors.affiliation: Universidad Nacional de Quilmes, Roque Saenz Peña 352, B1876BXD Bernal, Argentina.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fernandez-Alberti
mesh_terms: D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands