Format

Send to

Choose Destination
Nucleic Acids Res. 2016 Jan 4;44(D1):D308-12. doi: 10.1093/nar/gkv1279. Epub 2015 Nov 20.

UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures.

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
2
Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Structural and Computational Biology and Molecular Biophysics, Houston, TX 77030, USA.
4
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX 77030, USA.
5
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA Department of Structural and Computational Biology and Molecular Biophysics, Houston, TX 77030, USA Computational and Integrative Biomedical Research Center, Baylor College of Medicine, Houston, TX 77030, USA Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030, USA lichtarge@bcm.edu.

Abstract

The structure and function of proteins underlie most aspects of biology and their mutational perturbations often cause disease. To identify the molecular determinants of function as well as targets for drugs, it is central to characterize the important residues and how they cluster to form functional sites. The Evolutionary Trace (ET) achieves this by ranking the functional and structural importance of the protein sequence positions. ET uses evolutionary distances to estimate functional distances and correlates genotype variations with those in the fitness phenotype. Thus, ET ranks are worse for sequence positions that vary among evolutionarily closer homologs but better for positions that vary mostly among distant homologs. This approach identifies functional determinants, predicts function, guides the mutational redesign of functional and allosteric specificity, and interprets the action of coding sequence variations in proteins, people and populations. Now, the UET database offers pre-computed ET analyses for the protein structure databank, and on-the-fly analysis of any protein sequence. A web interface retrieves ET rankings of sequence positions and maps results to a structure to identify functionally important regions. This UET database integrates several ways of viewing the results on the protein sequence or structure and can be found at http://mammoth.bcm.tmc.edu/uet/.

PMID:
26590254
PMCID:
PMC4702906
DOI:
10.1093/nar/gkv1279
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center