Theory of binless multi-state free energy estimation with applications to protein-ligand binding.

ABSTRACT: The weighted histogram analysis method (WHAM) is routinely used for computing free energies and expectations from multiple ensembles. Existing derivations of WHAM require observations to be discretized into a finite number of bins. Yet, WHAM formulas seem to hold even if the bin sizes are made arbitrarily small. The purpose of this article is to demonstrate both the validity and value of the multi-state Bennet acceptance ratio (MBAR) method seen as a binless extension of WHAM. We discuss two statistical arguments to derive the MBAR equations, in parallel to the self-consistency and maximum likelihood derivations already known for WHAM. We show that the binless method, like WHAM, can be used not only to estimate free energies and equilibrium expectations, but also to estimate equilibrium di

SUBMITTER: Tan Z 

PROVIDER: S-EPMC3339880 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature