Comparative molecular dynamics simulation study of aquaporin Z.

• Main Author: Ching, April Shi Min.
• Other Authors: Mu, Yuguang
• Format: Final Year Project
• Language: English
• Published: 2009
• Subjects: DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/16349
• Institution: Nanyang Technological University

The structural and functional divergence between two 30 ns simulations of aquaporin Z in a solvated membrane, one using the General AMBER force field and the other a modified GROMOS-87 force field, ffgmx, was determined. The protein in the AMBER run displayed water transport activity and typical water-protein interaction. The simulation using ffgmx, despite an outwardly normal structure, did not have any water transport activity as a result of channel occlusion. The channel was blocked essentially permanently at the cytoplasmic end by a deformed loop B, due to a loss of constraining hydrogen bonds. Reversible and transient constrictions also arise at the selectivity filter as a result of artificially elevated side chain motion of its constituent residues and loss of important stabilising Van der Waals contacts – most significant is the aromatic side chain of Phe-43 whose face becomes perpendicular to the channel axis. These observations highlighted the deficiencies of the ffgmx/Berger force field combination in preserving critical hydrophobic contacts and hydrogen bonds in flexible moieties.