No abstract

We used the crystal structure of prolyl oligopeptidase (POP) with bound Z-pro-prolinal (ZPP) inhibitor (Protein Data Bank (PDB) structure 1QFS) to perform an intensive molecular dynamics study of the POP-ZPP complex. We performed 100 ns of simulation with the hemiacetal bond, through which the ZPP is bound to the POP, removed in order to better investigate the binding cavity environment. From basic analysis, measuring the radius of gyration, root mean square deviation, solvent accessible surface area and definition of the secondary structure of protein, we determined that the protein structure is highly stable and maintains its structure over the entire simulation time. This demonstrates that such long time simulations can be performed without the protein structure losing stability. We found that water bridges and hydrogen bonds play a negligible role in binding the ZPP thus indicating the importance of the hemiacetal bond. The two domains of the protein are bound by a set of approximately 12 hydrogen bonds, specific to the particular POP protein.

No abstract

Results from extensive 70 ns all-atom molecular dynamics simulations of catechol-Omethyltransferase (COMT) enzyme are reported. The simulations were performed with explicit TIP3P water and Mg 2þ ions. Four different crystal structures of COMT, with and without different ligands, were used. These simulations are among the most extensive of their kind and as such served as a stability test for such simulations. On the methodological side we found that the initial energy minimization procedure may be a crucial step: particular hydrogen bonds may break, and this can initiate an irreversible loss of protein structure that becomes observable in longer time scales of the order of tens of nanoseconds. This has important implications for both molecular dynamics and quantum mechanics-molecular mechanics simulations.