Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Molecular modeling and simulation approaches have been use to generate a complete model of the prokaryotic ABC transporter MsbA from Escherichia coli, starting from the low-resolution structure-based Calpha trace (PDB code 1JSQ). MsbA is of some biomedical interest as it is homologous to mammalian transporters such as P-glycoprotein and TAP. The quality of the MsbA model is assessed using a combination of molecular dynamics simulations and static structural analysis. These results suggest that the approach adopted for MsbA may be of general utility for generating all atom models from low-resolution crystal structures of membrane proteins. Molecular dynamics simulations of the MsbA model inserted in a fully solvated octane slab (a membrane mimetic environment) reveal that while the monomer is relatively stable, the dimer is unstable and undergoes significant conformational drift on a nanosecond time scale. This suggests that the MsbA crystal dimer may not correspond to the MsbA dimer in vivo. An alternative model of the dimer is discussed in the context of available experimental data.

Original publication

DOI

10.1021/bi027337t

Type

Journal article

Journal

Biochemistry

Publication Date

08/04/2003

Volume

42

Pages

3666 - 3673

Keywords

ATP-Binding Cassette Transporters, Bacterial Proteins, Binding Sites, Biological Transport, Computer Simulation, Crystallography, X-Ray, Dimerization, Drug Resistance, Microbial, Drug Resistance, Multiple, Escherichia coli, Escherichia coli Proteins, Lipid A, Membrane Proteins, Models, Molecular, Protein Conformation, Structure-Activity Relationship