Measuring evolutionary constraints as protein properties reflecting underlying mechanisms
Part 4. Bioinformatics
4.3. Protein Function and Annotation
Short Specialist Review
Published Online: 15 JUL 2005
Copyright © 2005 John Wiley & Sons, Ltd
Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics
How to Cite
Neuwald, A. F. and Liu, J. S. 2005. Measuring evolutionary constraints as protein properties reflecting underlying mechanisms. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 4:4.3:35.
- Published Online: 15 JUL 2005
Selective constraints are revealed in protein multiple sequence and structural alignments as conserved residues and corresponding atomic interactions. These patterns of conservation contain implicit information about underlying protein mechanisms, just as crystalline X-ray diffraction patterns contain implicit information about a protein's structure. Contrast hierarchical alignment and interaction network (CHAIN) analysis measures and characterizes selective constraints on the basis of co-conserved patterns and fits mechanistic models to these and other constraints. Just as the quantity and quality of X-ray diffraction patterns determines how well one can fit an atomic model to the inferred electron density, the quantity and quality of co-conserved patterns determines how well one can fit possible mechanisms to these inferred constraints. In principle, given sufficient data, biological mechanisms may be identified with high certainty. Nevertheless, even at “low resolution”, this information can prune the possibilities down to a manageable number for further experimental follow-up.
- Bayesian partitioning with pattern selection (BPPS);
- Markov chain Monte Carlo methods;
- CHAIN analysis;
- contrast hierarchical alignment