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MINOES: A new approach to select a representative ensemble of structures in NMR studies of (partially) unfolded states. Application to Δ25‐PYP
Author(s) -
Krzeminski Mickaël,
Fuentes Gloria,
Boelens Rolf,
Bonvin Alexandre M.J.J.
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22197
Subject(s) - a priori and a posteriori , conformational ensembles , nuclear magnetic resonance spectroscopy , chemistry , chemical shift , selection (genetic algorithm) , computer science , statistical physics , molecular dynamics , computational chemistry , physics , artificial intelligence , stereochemistry , philosophy , epistemology
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, Δ25‐PYP, which has been previously characterized by NMR (Bernard et al., Structure 2005;13:953–962). Proteins 2009. © 2008 Wiley‐Liss, Inc.