title: MINOES: a new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to Delta25-PYP.
abstract: In nature, some proteins partially unfold under specific environmental conditions. These unfolded states typically consist of a large ensemble of conformations; their proper description is therefore a challenging problem. NMR spectroscopy is particularly well suited for this task: information on conformational preferences can be derived, for example, from chemical shifts or residual dipolar couplings. This information, which is measured as a time- and ensemble-average, can be used to model these states by generating large ensembles of conformations. The challenge is then to select a minimum representative set of conformations out of a large ensemble to represent the unfolded state. We have developed for this purpose an algorithm called MINOES (MINimum Optimal Ensemble Selection), which is based on an iterative procedure based on a driven expansion/contraction selection process. MINOES aims at selecting an optimal and minimal ensemble of conformations that, on average, maximizes the agreement between back-calculated and experimental (NMR) data, without any a-priori assumption about the required ensemble size. This approach is demonstrated by modeling the partially unfolded state of a deletion mutant of the Photoactive Yellow Protein, Delta25-PYP, which has been previously characterized by NMR (Bernard et al., Structure 2005;13:953-962).
authors.affiliation: Bijvoet Center for Biomolecular Research, Science Faculty, Utrecht University, 3584 CH Utrecht, The Netherlands.
authors.forename: Mickaël
authors.initials: M
authors.lastname: Krzeminski
authors.forename: Gloria
authors.initials: G
authors.lastname: Fuentes
authors.forename: Rolf
authors.initials: R
authors.lastname: Boelens
authors.forename: Alexandre M J J
authors.initials: AM
authors.lastname: Bonvin
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D020283:Photoreceptors, Microbial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D012984:Software
chemical_list: D001426:Bacterial Proteins; D020283:Photoreceptors, Microbial; C050162:photoactive yellow protein, Bacteria