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Structure. 2015 Jul 7;23(7):1190-8. doi: 10.1016/j.str.2015.05.011. Epub 2015 Jun 18.

Parsimony in Protein Conformational Change.

Author information

1
Department of Biochemistry & Molecular Biology, Oregon Health & Science University, School of Medicine L-224, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
2
Department of Biochemistry, University of Utah, Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT 84112-5650, USA.
3
Department of Chemistry & Biochemistry, The Ohio State University, Newman and Wolfrom Laboratory, 100 West 18th Avenue, Columbus, OH 43210-1173, USA.
4
Department of Biochemistry & Molecular Biology, Oregon Health & Science University, School of Medicine L-224, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. Electronic address: chapmami@ohsu.edu.

Abstract

Protein conformational change is analyzed by finding the minimalist backbone torsion angle rotations that superpose crystal structures within experimental error. Of several approaches for enforcing parsimony during flexible least-squares superposition, an ℓ(1)-norm restraint provided greatest consistency with independent indications of flexibility from nuclear magnetic resonance relaxation dispersion and chemical shift perturbation in arginine kinase and four previously studied systems. Crystallographic cross-validation shows that the dihedral parameterization describes conformational change more accurately than rigid-group approaches. The rotations that superpose the principal elements of structure constitute a small fraction of the raw (φ, ψ) differences that also reflect local conformation and experimental error. Substantial long-range displacements can be mediated by modest dihedral rotations, accommodated even within α helices and β sheets without disruption of hydrogen bonding at the hinges. Consistency between ligand-associated and intrinsic motions (in the unliganded state) implies that induced changes tend to follow low-barrier paths between conformational sub-states that are in intrinsic dynamic equilibrium.

PMID:
26095029
PMCID:
PMC4497923
DOI:
10.1016/j.str.2015.05.011
[Indexed for MEDLINE]
Free PMC Article

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