PT  - JOURNAL ARTICLE
AU  - Samuel Bowerman
AU  - Joseph E. Curtis
AU  - Joseph Clayton
AU  - Emre H. Brookes
AU  - Jeff Wereszczynski
TI  - BEES: Bayesian Ensemble Estimation from SAS, a SASSIE-web Module
AID  - 10.1101/400168
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 400168
4099  - http://biorxiv.org/content/early/2018/08/25/400168.short
4100  - http://biorxiv.org/content/early/2018/08/25/400168.full
AB  - Many biomolecular complexes exist in a flexible ensemble of states in solution which are necessary to perform their biological function. Small angle scattering (SAS) measurements are a popular method for characterizing these flexible molecules due to their relative ease of use and ability to simultaneously probe the full ensemble of states. However, SAS data is typically low-dimensional and difficult to interpret without the assistance of additional structural models. In theory, experimental SAS curves can be reconstituted from a linear combination of theoretical models, although this procedure carries significant risk of overfitting the inherently low-dimensional SAS data. Previously, we developed a Bayesian-based method for fitting ensembles of model structures to experimental SAS data that rigorously avoids overfitting. However, we have found that these methods can be difficult to incorporate into typical SAS modeling workflows, especially for users that are not experts in computational modeling. To this end, we present the “Bayesian Ensemble Estimator from SAS” (BEES) program. Two forks of BEES are available, the primary one existing as module for the SASSIE webserver, and a developmental version that is a standalone python program. BEES allows users to exhaustively sample ensemble models constructed from a library of theoretical states and to interactively analyze and compare each model’s performance. The fitting routine also allows for a secondary data sets to be supplied, thereby simultaneously fitting models to both SAS data as well as orthogonal information. The flexible ensemble of K63-linked ubiquitin trimers is presented as an example of BEES’ capabilities.