Perspective on Free-Energy Perturbation Calculations for Chemical Equilibria

摘要: Abstract An overview is provided on the computation of free energy changes in solution using perturbation theory, overlap sampling, and related approximate methods. As a specific application, extensive results are for energies hydration substituted benzenes OPLS-AA force field explicit TIP4P water. For similar amount computer time, double-wide sampling methods yield very free-energy calculations. With standard protocols, average statistical uncertainty computed differences 0.1 - 0.2 kcal/mol. Application power-series expansion Peierls equation was also tested. Use first-order term generally reliable, while inclusion slowly-convergent, second-order fluctuation causes deterioration strongly hydrogen-bonded solutes.