The following features based on sequence conservation and protein structure were derived for 416 variants: average conservation scores of neighboring residues in 3D, number of neighbors, accessibility, and secondary structure.
The predictions, based solely on local structural similarity, are more accurate than those produced by ConSurf (Glaser et al., 2003, 2005), a protein surface mapping tool which depends upon sequence conservation and which to our knowledge, is the only available tool that maps sequence conservation to protein structure.
However, the conservation of protein structure across homologs often leads to uncontrolled cross-reactivity.
In light of the conservation of protein structure and degeneracy of sequence, SCOPE was developed to enable the "shuffling" of distantly related genes with no requirement for sequence identity.
To predict the functional relevance of other non-synonymous mutations in LATS1/2, we performed analyses of evolutionary conservation and protein structure through four different mutation-assessing methods: SIFT, PROVEAN, PolyPhen-2, and Mutation Assessor (Ng and Henikoff, 2003; Adzhubei et al., 2010; Reva et al., 2011; Choi et al., 2012).
This effect is due to the stable conservation of protein structure and architecture when compared to the coding sequence.
The sequence identity with yeast and human homologues for most of the ribosomal proteins were higher than 60%, which indicate conservation of protein structure and function.
This confirmed the incredible conservation of protein structure over massive evolutionary distances further supporting the notion that 3D structure could be exploited as an ancient fossil to detect family relationships.
The dN/ dS ratio data are consistent with evolutionary pressure for conservation of protein structure between all the orthologous pairs of BPI-like genes in cattle, human and mouse.
ProtTest v1.4 is based on the PhyML program [ 73] for maximum likelihood (ML) optimizations, and the best-fit model considers the relative rates of amino acid replacement and the evolutionary constraints imposed by conservation of protein structure and function.
