Comparative molecular dynamics simulation study of aquaporin Z.
Ching, April Shi Min.
Date of Issue2009
School of Biological Sciences
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.
DRNTU::Science::Biological sciences::Molecular biology
Final Year Project (FYP)
Nanyang Technological University