Free Energy by Molecular Simulation

Department of Chemistry, University of Houston, Houston, Texas, ( present address) High Performance Computational Chemistry Group, Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 993S2 

Relative free energies determine important chemical quantities such as relative affinities of binding of ligands to receptor molecules, relative solubilities, relative electrode potentials of different substances, adsorption coefficients, and chemical potentials. Thermodynamic cycle free energy methodologies have become one of the most popular tools in the computational study of complex chemical systems. 

Statistical mechanics forms the foundation of the methodological developments of the free energy difference techniques, providing the link between macroscopic, measurable quantities of chemical systems, and the detailed, microscopic description of the molecular system. The thermodynamic quantities of interest are expressed in terms of ensemble averages, phase space probabilities or partition functions, all of which eventually are determined by the system Hamiltonian. The main difficulty in practical calculations does not lie in 

Reviews in Computational Chemistry, Volume 9 Kenny B. Lipkowitz and Donald B. Boyd, Editors VCH Publishers, Inc. New York, 1996 

This chapter reviews some theoretical aspects of the two most popular free energy difference methods, thermodynamic perturbation and thermodynamic integration, as well as assumptions and approximations made in the implementation. Advantages and disadvantages of certain implementations are discussed, and general recommendations are given for the practical application of these methods. 

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Straatsma T P 1996. Free Energy by Molecular Simulation. In Lipkowitz K B and D B Boyd (Edito Reviews in Computational Chemistry Volume 9. New York, VCH Publishers, pp. 81-127. 

T. P. Straatsma, Free energy by molecular simulation, in Reviews in Computational... 

T. P. Straatsma, Free Energy by Molecular Simulation, in Reviews in Computational Chemistry, Vol. 9, K. B. Lipkowitz and D. B. Boyd, eds., VCH Publishers, New York, 1996, p. 81 H. Meirovitch, Calculation of the free energy and the entropy of macromol-ecular systems by computer simulation. Rev. in Computational Chem. 13, 1 (1998). 

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