Molecular fragment replacement

An alternative approach to obtaining a starting model for the refinement that does not need NOE data is called molecular fragment replacement [71] and treats the protein of interest as overlapping fragments of 7 to 10 residues in length. A protein database is... 

Fig. 8.11 Illustration of the basic steps followed by the Molecular Fragment Replacement method to build a model of the structure of the protein Dinl.

Kontaxis G, Delaglio F, Bax A. Molecular fragment replacement approach to protein structure determination by chemical 33. 

Delaglio F, Kontaxis G, Bax A (2000) Protein structure determination using molecular fragment replacement and NMR dipolar couplings. J Am Chem Soc 122 2142-2143... 

Figure 1.5 Bioisosteres. These are biologically equivalent molecular fragments that can be used to replace portions of a drug molecule.

Fig. 2.4. Product enumerations of a combinatorial library. For reaction-based enumeration, individual groups of —N(R1)(R2) and —(C0)-R3 are replaced by corresponding molecular fragments from reactants A and B. For template-based enumeration, the R-groups R1, R2, and R3 are replaced by independent lists of molecular fragments. Note that some combinations of R1 and R2 may not exist in component A for reaction-based enumerations. The template-based product structure with R-groups is also called Markush structure and its enumeration is called Markush enumeration or Markush exemplification.

The (I) - (II) conversion involves replacement of some ligand-bridged connections with terminal ligands, resulting in isolation of a molecular fragment of the non-molecular precursor. Many examples are found in the formation of cubanoid clusters (equation 8 M = Cu, Ag X = Cl, Br, I) ... 

When the constituent subsystems are mutually closed (in molecular fragment resolution), the corresponding matrices of charge sensitivities replace the global quantities in the corresponding four perturbation —> response transformations ... 

In a substitution, a molecular fragment of a reactant is replaced by a fragment of another reactant. A prominent example is the alkylation where an alkyl group is transferred from one molecule to another. E.g., the production of Ethylbenzene from Benzene and Ethylene by the so-called Priedel-Crafts alkylation is a standard process in chemical industry. " ... 

Crossover experiments often use methyl or other alkyl groups as labels. There is always the possibility, however, that a label may alter the course of a reaction. Therefore, the minimum label that will allow us to distinguish the reaction pathway is best, and an isotopic replacement is the smallest perturbation to the molecular structure we can envision. In the case of the Claisen reaction, labeling the allyl functionality of 34 with an isotope of carbon as shown in Figure 6.9 led to 35, but 36 was not detected. This result was further evidence that the mechanism does not involve molecular fragmentation, since a dissociative process would be expected to give both products. ... 

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