Umbrella sampling simulations of the closure of biotin carboxylase

Document Type

Conference Proceeding

Publication Date

1-1-2008

Abstract

Biotin carboxylase is a homodimer that utilizes ATP to carboxylate biotin. Solid state studies of the enzyme using x-ray crystallography revealed a prominent conformational change upon binding ATP. To determine the importance of this closing motion, the potential of mean force with the closure angle as a reaction coordinate was calculated using molecular dynamics simulations and umbrella sampling for a monomer of E. coli biotin carboxylase in water with restraints to simulate attachment to a surface. The result suggests that the most stable state for the enzyme is a closed state different from both the ATP bound and open state crystal structures. There is also a significant motion of a region near the dimer interface not predicted from the crystal structures which may have implications for the dynamics and activity of the dimer.

Publication Source (Journal or Book title)

Proceedings of 4th International Conference on Multiscale Materials Modeling, MMM 2008

First Page

688

Last Page

691

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