Evolutionary trace method

In the particular case of GPCRs, the application of CMA techniques, including the evolutionary trace method (181-183), has been aimed at the prediction of putative functionally important residues involved in GPCR-G protein interactions (170-175), GPCR-GPCR interactions (151,152,175,184-189), ligand-protein interactions (23,190,191), as well as signal transduction (170,192,193). 

Although the evolutionary trace method applied to GPCRs (175,185) fails to detect any residues responsible for the subtype-specific heterodimerizafion that has recently been demonstrated for opioid (96), somatostatin (106), and chemokine (98) receptors, correlated mutation analysis had already been demonstrated to be able to identify useful details of molecular specificity (184). Thus, the molecular basis of specificity was hypothesized to reside in outward (i.e., lipid) facing residues of TM5 and TM6 that exhibited evolutionarily correlated mutations and differed between receptor subtypes (184) in the case of dimerization. In the case of oligomers, the key interface between different subtypes was suggested to be the 2,3-interface (152) rather than the 5,6-interface. 

Lichtarge, O., Bourne, H. R., and Cohen, F. E. (1996) An evolutionary trace method defines binding surfaces common to protein families. J. Mol. Biol. 257, 342-358. 

Gkoutos, G. V., Higgs, C., Bywater, R. P Gouldson, P. R., and Reynolds, C. A. (1999) Evidence for dimerization in the p2-adrenergic receptor from the evolutionary trace method. Inti. J. Quantum. Chem. Biophys. Q. 74,371-379. 

Fortunately, in the past 10 years this approach has been developed to yield a number of automatic methods for predicting functional sites. The pioneer Evolutionary Trace method [35] (http //www-cryst.bioc.cam.ac.uk/ jiye/evoltrace/evol-trace.html) maps phylogenetic information onto structures and often reveals accurate information about functional regions. Many similar approaches have since been devised and applied in various contexts [36,37], and several are available over the Internet (e.g., JEvTrace [38], http //www.cmpharm.ucsf.edu/ marcinj/JEvTrace/). See Campbell et al. [39] for a timely review. 

Lichtarge, O., Sowa, M. E., and Philippi, A. (2002) Evolutionary traces of functional surfaces along G protein signaling pathway. Methods Enzymol. 344, 536-556. 

A method for detecting conserved residues, called evolutionary tracing (ET), was developed by lichtarge et al. [45], Several groups have embarked on developing methods for detecting functional sites based on ET and related methods (see... 

Sequence analysis has become a powerful tool in identifying functional domains in proteins. One such tool is the Evolutionary Trace (ET) method as developed and implemented by Lichtarge et One such study was on the... 

Figure 9. The residues identified by the Evolutionary Trace (ET) method on the external face of the receptor. In each orientation the helix/helices in focus are coloured mid grey while the ET residues in focus are coloured light grey. The remaining residues are dark grey, a) helices 5 and 6, b) helix 4, c) helices 2 and 3 d) helix7.

When co-crystal structures are not available, Ortiz et al. have suggested using functional residue prediction methods to identify selectivity residues [35]. The most popular of fhese mefhods are Evolutionary Trace [36] and ConSurf [37], which use phylogenetic trees to predict biologically-relevant residues that are then mapped onto a representative crystal structure. 

Evolutionary thought and theory since the time of Darwin have created a new function for taxonomic classification to provide a framework for the study of evolutionary relationships. The overwhelming evidence we have that all organisms on Earth are related by common descent from some of the first cells, has led to different methods for tracing the family trees or phylogenetic trees of living and fossil organisms. 

While known sequencing methods may enable the sequence or partial sequence to be established for an impure protein [e.g., cow milk lysozyme (White et al., 1988)], protein of high purity is required for other purposes (e.g., determination of trace lytic activity in an isolated a-lactalbumin or trace lactose synthase specifier activity in a lysozyme). Otherwise, erroneous conclusions may be drawn with respect to structure and function and their evolutionary relationships. 

The methods of the last chapter analyzed a sequence by its own virtues. We now turn to the comparison of two sequences. The rationales behind the comparison of sequences may be manifold. Above all, the theory of evolution tells us that gene sequences may have derived from common ancestral sequences. Thus it is of interest to trace the evolutionary history of mutations and other evolutionary changes. Comparison of biological sequences in this context is understood as comparison based on the criteria of evolu-... 

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