Inferring Structural Ensembles of Flexible and Dynamic Macromolecules Using Bayesian, Maximum Entropy, and Minimal-Ensemble Refinement Methods.

ABSTRACT

The flexible and dynamic nature of biomolecules and biomolecular complexes is essential for many cellular functions in living organisms but poses a challenge for experimental methods to determine high-resolution structural models. To meet this challenge, experiments are combined with molecular simulations. The latter propose models for structural ensembles, and the experimental data can be used to steer these simulations and to select ensembles that most likely underlie the experimental data. Here, we explain in detail how the "Bayesian Inference Of ENsembles" (BioEn) method can be used to refine such ensembles using a wide range of experimental data. The "Ensemble Refinement of SAXS" (EROS) method is a special case of BioEn, inspired by the Gull-Daniell formulation of maximum entropy image processing and focused originally on X-ray solution scattering experiments (SAXS) and then extended to integrative structural modeling. We also briefly sketch the "minimum ensemble method," a maximum-parsimony refinement method that seeks to represent an ensemble with a minimal number of representative structures.