computer modeling in molecular biology.pdf

234 Oliver S. Smartlink the eoc and pC1 conformations. The starting path was set to three copies of thepC2 conformation. Table 8-2 shows that this run converged to the same result as theeoc to pC2 trial, clearly demonstrating the dependence of the result on the initial setof moving positions taken. This dependence could be reduced by the use of a morepowerful optimization technique such as simulated annealing [49] - Table 8-2shows that the path with the higher peak energy has a higher objective function. Itis interesting to note that the final path does not approach the pC2 conformation- the closest position is r.m. s. 0.156 A with atom H2 being over l A from itsposition in pC2.Figure 8-6 shows the distinction between the two routes obtained for the transitionbetween the eoc and pC1 forms. The principle difference between the paths isthe behavior of the hydroxyl moiety H3-03. On the higher energy path this groupturns and points toward the divalent metal ion creating an unfavorable .interaction.In contrast the lower energy route has the dihedral angle 03-C3 changing in the oppositesense and the interaction between the hydroxyl group and the metal ion neverbecomes unfavorable.I & M’I$# M1Figure 8-6. A comparison of the routes taken by substrate atoms in the different paths obtainedfor the conformational change between the eoc (dark lines) and pC1 (open lines) formsin D-xylose isomerase. Part (a) shows the routes for the higher energy path obtained fromlinearly interpolated starting conformations and (b) shows the lower energy path obtained byusing the pC2 energy minimum for the starting conformations. In each case the transitionstate conformation is marked by grey lines and the routes through space taken by hydrogenand oxygen atoms are shown by thin and dashed lines respectively.