Accurate Structural Correlations from Maximum Likelihood Superpositions
By Douglas L. Theobald, Deborah S. Wuttke. 2008
105 citations recorded by the source corpus.
The cores of globular proteins are densely packed, resulting in complicated networks of structural interactions. These interactions in turn give rise to dynamic structural correlations over a wide range of time scales. Accurate analysis of these complex correlations is crucial for understanding biomolecular mechanisms and for relating structure to function. Here we report a highly accurate technique for inferring the major modes of structural correlation in macromolecules using likelihood-based statistical analysis of sets of structures. This method is generally applicable to any ensemble of related molecules, including families of nuclear magnetic resonance (NMR) models, different crystal forms of a protein, and structural alignments of homologous proteins, as well as molecular dynamics trajectories. Dominant modes of structural correlation are determined using principal components analysis (PCA) of the maximum likelihood estimate of the correlation matrix. The correlations we identify are inherently independent of the statistical uncertainty and dynamic heterogeneity associated with the structural coordinates. We additionally present an easily interpretable method (“PCA plots”) for displaying these positional correlations by color-coding them onto a macromolecular structure. Maximum likelihood PCA of structural superpositions, and the structural PCA plots that illustrate the results, will facilitate the accurate determination of dynamic structural correlations analyzed in diverse fields of structural biology.
Subfields: Materials Chemistry, Molecular Biology
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In Materials Chemistry
- David Baker
- Sergey Ovchinnikov
- Frank DiMaio
- Ivan V. Anishchenko
- Yifan Song
- Yang Zhang
- R. Wang
- Gaetano T. Montelione
In Molecular Biology
- David Baker
- Sergey Ovchinnikov
- Frank DiMaio
- Ivan V. Anishchenko
- Yang Zhang
- Yifan Song
- Tanja Kortemme
- R. Wang
Citations in the corpus
- De novo protein design by deep network hallucination (2020, methodology): “Structural alignments comparing NMR and crystal structures to halluci-nated models were performed using the Theseus maximum likelihood superpositioning tool 57 .”
- Automated structure refinement of macromolecular assemblies from cryo-EM maps using Rosetta (2016, methodology): “The per-residue structural variance of ensemble models is calculated using Theseus with the default command line ( Theobald and Wuttke, 2008 ).”
- Pervasive tertiary structure in the dengue virus RNA genome (2018, methodology): “The ten models from each cluster with the lowest free-energy were aligned using Theseus (23), and structure images were composed using Pymol (24).”