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 ?(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 (?, ?) differences that also reflect local conformation and experimental error. Substantial long-range displacements can be mediated by modest dihedral rotations, accommodated even within ? helices and ? 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.

SUBMITTER: Chapman BK 

PROVIDER: S-EPMC4497923 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature