computer modeling in molecular biology.pdf

4 Molecular Dynamics and Free Energy Calculations 89dG(A 'B)1 A62s2f A63s3f A64s4f AC5s5f AC6S6Figure 4-16. Schematic representation of the pathway used for the Ile + Ala alchemicaltransformation. The pathway between the end states A (Ile) and B (Ala) is defined by six intermediatestates labelled S1 -S6. These states are generated by gradually modifying van derWaals parameters and bond lengths of the sidechain representing state A in the sidechainrepresenting state B (see Prkvost et al. for details [13]). The overall free energy difference iscomputed as the sum of the free energy differences between successive states along thisIpathway (AGj), yielding AG(A-,B) = AGj.j=l516). Individual L~G~,~,~ values were then summed to give the overall free energydifference for the transformation. This corresponds to taking discrete points alonga pathway between A and B that is described by a non-linear hybrid potential, andperforming a linear interpolation between these points using the classical procedure.4.3.2.2 The Molecular Systems and Simulation ProcedureThe ensemble averages over configuration space required for Eqs. (4-13) and (4-15)were computed at room temperature (300 K) using a time saving molecular dynamicsprocedure called Stochastic Boundary Molecular Dynamics (SBMD) [95]. This pro-