Zipping and unzipping of adenylate kinase: atomistic insights into the ensemble of open<-->closed transitions.

ABSTRACT: Adenylate kinase (AdK), a phosphotransferase enzyme, plays an important role in cellular energy homeostasis. It undergoes a large conformational change between an open and a closed state, even in the absence of substrate. We investigate the apo-AdK transition at the atomic level both with free-energy calculations and with our new dynamic importance sampling (DIMS) molecular dynamics method. DIMS is shown to sample biologically relevant conformations as verified by comparing an ensemble of hundreds of DIMS transitions to AdK crystal structure intermediates. The simulations reveal in atomic detail how hinge regions partially and intermittently unfold during the transition. Conserved salt bridges are seen to have important structural and dynamic roles; in particular, four ionic bonds that ope

SUBMITTER: Beckstein O 

PROVIDER: S-EPMC2803350 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature