Structure determination homology methods

The molecular replacement method assumes similarity of the unknown structure to a known one. This is the most rapid method but requires the availability of a homologous protein s structure. The method relies on the observation that proteins which are similar in their amino acid sequence (homologous) will have very similar folding of their polypeptide chains. This method also relies on the use of Patterson functions. As the number of protein structure determinations increases rapidly, the molecular replacement method becomes extremely useful for determining protein phase angles. 

Compounds of this homologous series with n > 1 exist and have been analyzed by neutron diffraction methods. More specifically, precise structural determinations of La gCa OujOg (27)(28) and La19Sr11Cu2Oe (27) have been carried out and have shown that the sequence of layers, their composition, and the general distribution of the atoms in the unit cell are entirely consistent with the scheme of Figure 9. The structural parameters of the calcium compound are given in Table 8. We may write the sequence of layers for these two compounds as... 

The molecular replacement method used for protein structure determination (50,51) involves determining the orientation and the position in the unit cell of a known structure such as that of a homologous protein that has previously been determined or the same protein in a different unit cell (a polymorph). For the rotation function the Patterson map is systematically laid down upon itself in all possible orientations (Fig. 23). Six parameters that define the position and orientation of the protein in the unit cell are found from maxima in a function that describes the extent of overlap between the two placements of the Patterson function. This function will reveal the relative orientations of protein molecules in the unit cell. The rotation function is thus a computational tool used to assess the agreement or degree of coincidence of two Patterson functions, one from a model and the other from the diffraction pattern. 

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