Homologous proteins multiple sequence alignment

Fig. 3.9. Three-dimensional G protein-coupled CB2 receptor structure (right) constructed by homology and multiple sequence alignment...

Fig. 3.9. Three-dimensional G protein-coupled CB2 receptor structure (right) constructed by homology and multiple sequence alignment method (left), including the seven transmembrane helices (cylinders, l-VII) and loop regions (ribbons) (See color plate.) (From Xie XQ, Chen JZ, Billings EM. 3D structural model of the G protein-coupled...

Although the overall accuracy of secondary structure prediction is significantly improved with the PHDsec design, not all proteins can be equally well predicted. Worst predicted proteins are those with unusual features and those with bad sequence alignments. When information about homologous proteins is not available (i.e., no multiple sequence alignment), the predictive accuracy may be reduced by about 10%. 

Multiple sequence alignment of BACE family members and human pepsin (Protein Data Bank entry Ipso, used as the basis of homology modeling). Identical residues are shaded gray, highly conserved residues in yellow, and active-site residues in the model in contact with the peptide substrate are indicated by an asterisk ( ). BACE residue Arg 296, which is most often serine or threonine at this position in... 

In summary, there is no simple correlation between the occurrence of peripheral ion pairs and thermal stabilization. Even after carefiil selection of specific loci for site-directed mutagenesis on the basis of multiple sequence alignments and homology modeling, the results are not clearly predictable. If we recall that the overall stability of proteins is a minute difference between large contributions of attractive and repulsive forces and the corresponding entropy contributions, this result is not surprising. 

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