Methods molecular replacement

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. 

Rossmann, M.G. The Molecular Replacement Method. Gordon Breach, New York, 1972. 

The integrated molecular replacement method comparison of automatic protocols... 

Crowther, R. A. (1972). The fast rotation function. In The Molecular Replacement Method, Rossmann, M. G., ed. Gordon and Breach, New York, pp. 173-185. 

Rossmann, M. G. (1990) The molecular replacement method. Acta Crystallogr. A 46, 73-82. 

Rayment, I. (1983). Molecular replacement method at low resolution optimum strategy and intrinsic limitations as determined by calculations on icosahedral virus models. Acta Crystallogr. A 39,102-116. 

Molecular Replacement. The tertiary structure of crystalline ALBP was solved by using the molecular replacement method incorporated into the XPLOR computer program (Brunger et al., 1987). The refined crystal structure of myelin P2 protein without solvent and fatty acid was used as the probe structure throughout the molecular replacement studies. We are indebted to Dr. A. Jones and his colleagues for permission to use their refined P2 coordinates before publication. 

It is now better known as Molecular Replacement Method. Michael Rossmann and David Blow working in Cambridge, England rediscovered the method... 

The molecular replacement method is often used for protein structure determination. It involves determining the orientation and the position of the known structure (or a portion of the structure) with respect to the crystallographic axes three angles describe the orientation... 

Molecular replacement method The use of rotation and translation functions (q.v.), of noncrystallographic symmetry (q.v.), or of structural information from related structures, to determine a protein crystal structure. 

Determine relative phases by isomorphous replacement methods and calculate an electron-density map. Alternatively use molecular replacement methods to determine the structure and calculate an electron-density map. 

Interactions at High Resolution. P S Biomedical Sciences Symposia., 1985. Crowther, R.A., In The Molecular Replacement Method (Rossman, M.G. ed.). New York Gordon Breach (1972) 173. 

Molecular replacement is usually straightforward and performed within minutes. However, when only low resolution data and a poor search model are available, model bias can become an issue and experimental phasing may be needed. Nevertheless, the molecular replacement method is extremely useful in the context of structure-based design where it is used to expedite the determination of multiple protein complexes or to analyze, in an automated way, multiple data sets from a fragment-based screen. 

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. 

Rossmann, M.G. (1972) Molecular Replacement Method, New York Gordon and Breach. 

Alternative ways of exploiting the information in a Patterson map are known as molecular replacement methods, being able to locate structural fragments and using this initial phase information to proceed as in the case of heavy atoms. 

The crystal structure of turkey egg-white lysozyme, determined by the molecular replacement method at 5 A resolution, has now been refined to 2.8 A resolution and a model has been built to fit the electron density. A comparison of the co-ordinates with those of the hen enzyme was made a significant difference was observed in the region of residues 98-115 of the structure. The interactions between various saccharides bound at subsites E and F and the enzyme molecules were discussed. 

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