Automated identification of functional dynamic contact networks from X-ray crystallography.

ABSTRACT: Protein function often depends on the exchange between conformational substates. Allosteric ligand binding or distal mutations can stabilize specific active-site conformations and consequently alter protein function. Observing alternative conformations at low levels of electron density, in addition to comparison of independently determined X-ray crystal structures, can provide mechanistic insights into conformational dynamics. Here we report a new algorithm, CONTACT, that identifies contact networks of conformationally heterogeneous residues directly from high-resolution X-ray crystallography data. Contact networks determined for Escherichia coli dihydrofolate reductase (ecDHFR) predict the observed long-range pattern of NMR chemical shift perturbations of an allosteric mutation. A compari

SUBMITTER: van den Bedem H 

PROVIDER: S-EPMC3760795 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature