On the Use of Interaction Entropy and Related Methods to Estimate Binding Entropies.

ABSTRACT: Molecular mechanics combined with Poisson-Boltzmann or generalized Born and solvent-accessible area solvation energies (MM/PBSA and MM/GBSA) are popular methods to estimate the free energy for the binding of small molecules to biomacromolecules. However, the estimation of the entropy has been problematic and time-consuming. Traditionally, normal-mode analysis has been used to estimate the entropy, but more recently, alternative approaches have been suggested. In particular, it has been suggested that exponential averaging of the electrostatic and Lennard-Jones interaction energies may provide much faster and more accurate entropies, the interaction entropy (IE) approach. In this study, we show that this exponential averaging is extremely poorly conditioned. Using stochastic simulations, as

SUBMITTER: Ekberg V 

PROVIDER: S-EPMC8389774 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature