title: Parsimony in Protein Conformational Change.
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.
authors.affiliation: 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.
authors.forename: Brynmor K
authors.initials: BK
authors.lastname: Chapman
authors.affiliation: 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.
authors.forename: Omar
authors.initials: O
authors.lastname: Davulcu
authors.affiliation: Department of Biochemistry, University of Utah, Emma Eccles Jones Medical Research Building, 15 North Medical Drive East, Salt Lake City, UT 84112-5650, USA.
authors.forename: Jack J
authors.initials: JJ
authors.lastname: Skalicky
authors.affiliation: Department of Chemistry & Biochemistry, The Ohio State University, Newman and Wolfrom Laboratory, 100 West 18th Avenue, Columbus, OH 43210-1173, USA.
authors.forename: Rafael P
authors.initials: RP
authors.lastname: Brüschweiler
authors.affiliation: 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.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Chapman
mesh_terms: D001122:Arginine Kinase / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D001122:Arginine Kinase