CONVERGENCE PROPERTIES OF FREE ENERGY CALCULATIONS : ALPHA -CYCLODEXTRIN COMPLEXES AS A CASE STUDY

摘要: By considering all possible mutations among four para-substituted phenols, p-chlorophenol, p-methylphenol, p-cyanophenol, and p-methoxyphenol, which bind as inclusion compounds in alpha-cyclodextrin, the convergence properties of thermodynamic integration free energy calculations using slow growth compared to numerical quadrature are investigated interpreted terms structural dynamical molecular system. It is shown that a systematic increase calculated hysteresis can be expected with increasing simulation time slow-growth if system perturbed faster than rate at various states make up equilibrium ensemble sampled. Using effects nonequilibrium largely separated from insufficient sampling. shown, however, apparent degree when does not necessarily reflect accuracy calculation. The utility formulating closed cycles both bound unbound means determining minimum error given calculation demonstrated. choice pathway scheme on within also discussed. Finally, quality force field used relative importance opposed sampling considerations assessed by comparing estimated differences experimental data. meaningful appraisal specific cannot made independent considerations. A modification GROMOS improved agreement between energies for mutation p-chlorophenol p-methylphenol proposed.