Fragment matching

An important step according to several de novo design concepts is fragment matching on a query structure. This requires fragment representations that are... 

Figure 7.6 Fragment generation and matching using the Shapelets approach, (a) A molecular fragment is described by its Shapelets (paraboloids) decomposition of the solvent-accessible surface (mesh), (b) Result of fragments matching to a reference structure. A benzamidine building-block was matched to a thrombin inhibitor by Shapelets-mdiic g.

Once ACCS subset is assigned to a specific activity class, characteristic substructures are mapped back on each molecule by performing a subgraph search for each fragment and whenever a fragment matches an atom of the molecule, a counter for that atom is increased by 1. For each atom, division of its final counter state by the total number of matched substructures gives its match rate. Then, for each active molecule, core structures are defined as the set of all atoms of the molecule that have an ACCS match rate greater than a threshold value. 

The largest difference between force fields is probably how they handle electrostatics. Each force field uses its own definition of what functions and data should be used. The well-known MM2 force field describes all electrostatic interactions by bond dipoles (4), but most other force fields utilize atomic point charges. The charges may in turn be obtained from fragment matching (34), from bond-type-dependent charge flux (35), or from more complex schemes that can also respond to the environment (36). 

In addition, a proteolytic activity was detected apparently synthesized in the cell-free system, which cleaved the coat precursor polypeptide of the virus into fragments matching in size the virus coat proteins produced in infected cells. In agreement with the results discussed for poliovirus, the results tend to rule out an autoproteolytic activity associated with the coat proteins. This is in conflict with an earlier study on EMC virus proteolysis (37) > in which coat polypeptide gamma, co-purified with an endo proteolytic activity. 

S. Molodtsov. The generation of molecular graphs with obligatory, forbidden and desirable fragments. MATCH Common. Math. Comput. Chem., 37 157-162,1998. 

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