Bayesian multiple protein structure alignment

Multiple protein structure alignment is an important tool in computational biology, with numerous algorithms published in the past two decades. However, recently literature highlights a growing recognition of the inconsistencies among alignments from different algorithms, and the instability of alignments obtained by individual algorithms under small fluctuations of the input structures. Here we present a probabilistic model-based approach to the problem of multiple structure alignment, using an explicit statistical model. The resulting algorithm produces a Bayesian posterior distribution over alignments which accounts for alignment uncertainty arising from evolutionary variability, experimental noise, and thermal fluctuation, as well as sensitivity to alignment algorithm parameters. We demonstrate the robustness of this approach on alignments identified previously in the literature as "difficult" for existing algorithms. We also show the potential for significant stabilization of tree reconstruction in structural phylogenetics. © 2014 Springer International Publishing Switzerland.

Duke Scholars

Author Scott C. Schmidler Statistical Science