Origin of mechanical strength of bovine carbonic anhydrase studied by molecular dynamics simulation.

ABSTRACT: The forced unfolding process of bovine carbonic anhydrase II (BCA II) was examined at the atomic level by the molecular dynamics (MD) simulation. By force spectroscopy, experimentally obtained force-extension curves (F-E curves) showed a prominent force peak after 50 nm extension. F-E curves obtained from our simulation had three force peaks appearing after extensions of 10-17 nm, 40 nm, and 53 nm, each signifying a brittle fracture of a specific local structure. Upon undergoing the final fracture at 53 nm of extension, the entire molecule became a single flexible chain and was further extended to its full theoretical length, almost as a random coil. This feature of the 53-nm peak strongly suggested its close correspondence to the experimentally observed force peak at approximately 60-nm extension. The 53-nm peak in the molecular dynamics simulation corresponded to the unfolding process of the beta-sheeted core that includes zinc-coordinating histidine residues. These results suggest that the structural change occurring at 50-60 nm in atomic force microscopy experiments corresponded to the destruction of the zinc coordination site.

SUBMITTER: Ohta S 

PROVIDER: S-EPMC1304910 | biostudies-literature | 2004 Dec

REPOSITORIES: biostudies-literature