PBSA Applied to Computer-Assisted Ligand Design

MM-PBSA Applied to Computer-Assisted Ligand Design 

Bemd Kuhn Oreola Donini, Shuanghong Huo Junmei Wang+, and Peter A. Kollman+ 

The MM-PBSA approach assumes that the free energy G of a macromolecular system in solution can be adequately approximated by Equation 1 

In the following, we give a brief description on how to evaluate the various terms in Equation 1. A more extensive summary of the computational details typically used in our studies as well as the CPU requirements of the MM/PBSA approach can be found elsewhere.11 Emm simply evaluates the average potential energy of the system using the same force field (e.g. Equation 3 of Cornell et al.)12 as used to propagate the molecular dynamics trajectory. 

When one employs Equation 2 using only the complex trajectory, the internal energy contributions cancel and only the non-bonded terms (van der Waals and electrostatic) between ligand and macromolecule contribute to AG . However, if one runs separate trajectories of C, M, and L, all the terms in Equation 3 will contribute to AG . 

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B. Kuhn, O. Donini, S. Huo, J. Wang, and P. A. Kollman, MM-PBSA applied to computer-assisted ligand design, in Free Energy Calculations in Rational Drug Design, M. R. Reddy and M. D. Erion, eds., Kluwer/Plenum Press, New York (2001), pp. 243-251. 

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