title: 600 ps molecular dynamics reveals stable substructures and flexible hinge points in cAMP dependent protein kinase.
abstract: Molecular dynamics simulations of the catalytic subunit of cAMP dependent protein kinase (cAPK) have been performed in an aqueous environment. The relations among the protein hydrogen-bonding network, secondary structural elements, and the internal motions of rigid domains were examined. The values of fluctuations of protein dihedral angles during dynamics show quite distinct maxima in the regions of loops and minima in the regions of alpha-helices and beta-strands. Analyses of conformation snapshots throughout the run show stable subdomains and indicate that these rigid domains are constrained during the dynamics by a stable network of hydrogen bonds. The most stable subdomain during the dynamics was in the small lobe including part of the carboxy-terminal tail. The most significant flexible region was the highly conserved glycine-rich loop between beta strands 1 and 2 in the small lobe. Many of the main chain dihedral angle changes measured in a comparison of the crystallographic structures of "open" and "closed" conformations of cAPK correspond to the highly flexible residues found during dynamics.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0654, USA.
authors.forename: I
authors.initials: I
authors.lastname: Tsigelny
authors.forename: J P
authors.initials: JP
authors.lastname: Greenberg
authors.forename: S
authors.initials: S
authors.lastname: Cox
authors.forename: W L
authors.initials: WL
authors.lastname: Nichols
authors.forename: S S
authors.initials: SS
authors.lastname: Taylor
authors.forename: L F
authors.initials: LF
authors.lastname: Ten Eyck
mesh_terms: D000818:Animals; D003198:Computer Simulation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases