Abstract
To estimate free energy differences from a single simulation of the initial state one may either, use a series expansion of the free energy around the initial state, make an assumption in regard to the functional form of the free energy or treat the mutation as a single step perturbation. Of these the perturbation approach holds the greatest promise. The perturbation approach is fast, easy to implement and does not depend on empirically derived parameters or assumptions. Given an appropriate reference state the perturbation approach can be used to rapidly estimate solvation or binding free energies of a wide range of related compounds for use in force field development or structure based drug design.
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Mark, A.E., Schäfer, H., Liu, H., van Gunsteren, W. (1999). Estimating Relative Free Energies from a Single Simulation of the Initial State. In: Deuflhard, P., Hermans, J., Leimkuhler, B., Mark, A.E., Reich, S., Skeel, R.D. (eds) Computational Molecular Dynamics: Challenges, Methods, Ideas. Lecture Notes in Computational Science and Engineering, vol 4. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58360-5_8
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DOI: https://doi.org/10.1007/978-3-642-58360-5_8
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