computer modeling in molecular biology.pdf

72 Shoshana .l Wodak, Daniel van Belle, and Martine Prt-vostaway from the crystal structure have occurred during the thermalization andequilibration periods that precede the production run. Thereafter, only a smalloverall drift is observed, with fluctuations of the order of 0.3 A. The backbone rmsdof the average protein conformation computed from the entire 250 ps trajectory is1.2 A, and that of all the atoms (including aliphatic hydrogens) is 1.7 A.The rmsd values obtained in the present simulations are among the lowest valuesreported so far for simulations of solvated proteins where rmsd of C, atoms usuallyrange around 1.4-1.9 A [23-261. Somewhat smaller rmsd values (1.18 A) wererecently reported for the non-hydrogen atoms of BPTI in a 200 ps MD simulationP21.Inspection of the deviations between the backbone atoms in the average simulatedprotein conformation and the crystal structure (Figure 4-6) shows that the largestdeviations occur in regions that participate in crystal contacts. These regions arelocated at the N terminus and in three loops: the loop preceding the second a-helix,the loop between /3-strands 2 and 3 and that between strands 4 and 5. As expected,residues belonging to the &sheet, which are involved in numerous tertiary interactionsdisplay the lowest deviations (rmsd- 0.6 A). The deviations displayed by therecognition loop (residues 54-60) are intermediate in range, with the largest one(-2.0 A) exhibited by residue Lys 57. The near uniform 1 A displacement ofresidues 6-17 in the first a-helix, represent a rigid-body movement of this helixrelative to the P-sheet.Figure 4-6. Deviations (in A) of Ca atoms of the 250 ps average conformation of barnasefrom the crystal structure, as a function of their position N, along the sequence. Bars indicatethe limits of secondary structure elements, and stars indicate residues involved in intermolecularcontacts in the barnase crystal. Both are displayed below the abscissa.