10.1021/acs.jctc.7b00059.s001
Samuel Bowerman
Samuel
Bowerman
Ambar S.J.B. Rana
Ambar S.J.B.
Rana
Amy Rice
Amy
Rice
Grace H. Pham
Grace H.
Pham
Eric R. Strieter
Eric R.
Strieter
Jeff Wereszczynski
Jeff
Wereszczynski
Determining Atomistic SAXS Models of Tri-Ubiquitin
Chains from Bayesian Analysis of Accelerated Molecular Dynamics Simulations
American Chemical Society
2017
Bayesian Analysis
multistate ensembles
solution ensemble
iterative Bayesian Monte Carlo method
quality models
linkage type
solution flexibility
solution states
linkage site
Atomistic SAXS Models
Tri-Ubiquitin Chains
ubiquitin trimers
MD simulations
time scales
Molecular Dynamics Simulations Small-angle X-ray
2017-05-08 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Determining_Atomistic_SAXS_Models_of_Tri-Ubiquitin_Chains_from_Bayesian_Analysis_of_Accelerated_Molecular_Dynamics_Simulations/5011988
Small-angle X-ray
scattering (SAXS) has become an increasingly
popular technique for characterizing the solution ensemble of flexible
biomolecules. However, data resulting from SAXS is typically low-dimensional
and is therefore difficult to interpret without additional structural
knowledge. In theory, molecular dynamics (MD) trajectories can provide
this information, but conventional simulations rarely sample the complete
ensemble. Here, we demonstrate that accelerated MD simulations can
be used to produce higher quality models in shorter time scales than
standard simulations, and we present an iterative Bayesian Monte Carlo
method that is able to identify multistate ensembles without overfitting.
This methodology is applied to several ubiquitin trimers to demonstrate
the effect of linkage type on the solution states of the signaling
protein. We observe that the linkage site directly affects the solution
flexibility of the trimer and theorize that this difference in plasticity
contributes to their disparate roles in vivo.