ct7b00059_si_001.pdf (6.31 MB)
Determining Atomistic SAXS Models of Tri-Ubiquitin Chains from Bayesian Analysis of Accelerated Molecular Dynamics Simulations
journal contribution
posted on 2017-05-08, 00:00 authored by Samuel Bowerman, Ambar S.J.B. Rana, Amy Rice, Grace H. Pham, Eric R. Strieter, Jeff WereszczynskiSmall-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.