Dynamical network of residue-residue contacts reveals coupled allosteric effects in recognition, catalysis, and mutation.

ABSTRACT: Detailed understanding of how conformational dynamics orchestrates function in allosteric regulation of recognition and catalysis remains ambiguous. Here, we simulate CypA using multiple-microsecond-long atomistic molecular dynamics in explicit solvent and carry out NMR experiments. We analyze a large amount of time-dependent multidimensional data with a coarse-grained approach and map key dynamical features within individual macrostates by defining dynamics in terms of residue-residue contacts. The effects of substrate binding are observed to be largely sensed at a location over 15 Å from the active site, implying its importance in allostery. Using NMR experiments, we confirm that a dynamic cluster of residues in this distal region is directly coupled to the active site. Furthermore, the

SUBMITTER: Doshi U 

PROVIDER: S-EPMC4855540 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature