Convergence Behavior in Free Energy Simulations

Abstract

Free energy perturbation (FEP) simulations offer much promise for understanding site specific mutagenesis in protein engineering experiments and for rational drug design. These calculations can in principle yield the free energy difference between two states (for example a native and mutant protein) and some quite promising results have been obtained using the FEP technique. However much work remains to be done on accessing the accuracy and limitations of these calculations before they can be used on a routine basis [1]. Many of the problems occur because there is a complicated potential energy surface describing the two states in the calculation.

Key Words:

• Free energy perturbation method
• local minima
• computer simulation