computer modeling in molecular biology.pdf

4 Molecular Dynamics and Free Energy Calculations 714.2.2 Analysis of the 250 ps Trajectory of Barnasein Water4.2.2.1 Protein MotionAnalysis of the movements displayed by the protein structure during the MD simulationis always quite revealing. Such movements can be measured by computing thedeviations of the atomic positions between conformations generated in the simulationand a reference state, usually taken to be the crystal structure. To eliminate contributionsfrom the rigid-body tumbling and translational motion of the entire molecule,these deviations are computed after performing coordinate superpositions [52].Large structural deformations uniformly distributed across the 3D structure couldresult from shortcomings in the potential functions or from inadequate simulationconditions. Significant localized deformations could be due to such problems aswell, but may also represent structural re-adjustments that occur in certain regionsupon transfer from the crystalline environment to solution conditions, or reflect theinherent local flexibility of such regions.The root mean square deviation (rmsd) of the backbone atoms of individual conformationsof barnase along the 250 ps strajectory is displayed in Figure 4-5. Thisrmsd, measured relative to the starting crystal conformation, displays a value ofabout 1.2 A at the beginning of the trajectory (t = 0), indicating that movements1.63 1.2t (PS)0.00 50 100 . 150 200 250 4 ~Figure 4-5. Root mean square deviations (rmsd) of barnase backbone atoms in conformationsalong the 250 ps molecular dynamics trajectory of the protein-water system. The rmsdvalues are computed relative to the barnase crystal structure after coordinate superposition(McLachlan [52]). The significant rmsd value at t = 0, reflects movements in the structure thatoccurred during the thermalization and equilibration phases that precede the 250 ps productionperiod (see text).