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

¹ Tokyo Institute of Technology
² Rajshahi University

^* To whom correspondence should be addressed. E-mail: aikai{at}bio.titech.ac.jp.

Submitted on May 1, 2004
Revised on June 10, 2004
Accepted on 7 September 2004

	Abstract

The forced unfolding process of bovine carbonic anhydrase II (BCA II) was examined at the atomic level by the molecular dynamics 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 the present 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 around 60 nm extension. The 53 nm peak in the MD simulation corresponded to the unfolding process of the -sheeted core that includes zinc coordinating histidine residues. These results suggest that the structural change occurring at 50-60 nm in AFM experiments corresponded to the destruction of the zinc coordination site.

Key Words: beta sheet, carbonic anhydrase, explicit and implicit solvent, force-extension curve, steered molecular dynamics simulation, unfolding

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