Predictive fragmentation software

Fig. 1.41 (A) Product ion spectrum of remikiren obtained on a QqTOF. (B) Software-predicted fragments (Mass Frontier, HighChem) for the ion at m/z 282.

A number of other software packages are available to predict NMR spectra. The use of large NMR spectral databases is the most popular approach it utilizes assigned chemical structures. In an advanced approach, parameters such as solvent information can be used to refine the accuracy of the prediction. A typical application works with tables of experimental chemical shifts from experimental NMR spectra. Each shift value is assigned to a specific structural fragment. The query structure is dissected into fragments that are compared with the fragments in the database. For each coincidence, the experimental chemical shift from the database is used to compose the final set of chemical shifts for the... 

In addition to software tools to help postacquisition processing, software tools to help mass spectral interpretation, particularly MS/MS, have taken new strides as well (Heinonen et al., 2008). One example of such a software tool is the MathSpec program. The details of the MathSpec approach have been explained (Sweeney, 2003). MathSpec software is used in conjunction with MS/MS spectra obtained under high-resolution conditions. The software systematically attempts to assemble possible parts (from the MS/MS fragment data) of the molecule into a rational molecule. Other examples of structure elucidation software include HighChem s Mass Frontier and ACD/Labs ACD/MS Manager (Bayliss et al., 2007). Other metabolite prediction software tools such as Meteor are also being incorporated into LC-MS software as tools to help accelerate metabolite detection and characterization (Testa et al., 2005 Ives et al., 2007). 

Meylan, W., P.H. Howard, and R.S. Boethling. 1992. Molecular topology/fragment contribution method for predicting soil sorption coefficients. Environ. Sci. Technol. 26(8) 1560-1567. PCK-OCWIN software version 1.61, Syracuse Research Corp, Syracuse, NY. 

The SRC program KOWWIN uses an atom/fragment contribution method to predict log Kow. This is a reductionist method (the fragment coefficients were derived by multiple regression from a development set of reliably measured log Kow values). The other main software tool, ClogP for Windows (Leo, 1993) is a constructionist method (the fragment coefficients are evaluated from the simplest examples in which they occur). Both methods have a high level of accuracy and are widely accepted as the best tools available. 

Sayle has noticed that direct assignment of typical pK values according to detected ionizable atom types predicts pK values for simple molecules with standard deviation of 0.95 log units. The observation that similar molecules, or similar molecular fragments, have similar pK is the basis of the last class of methods. A database containing either complete structures or structural fragments and experimental pK values is searched for the nearest neighbors of the compound in question. Correction factors may be eventually applied to the observed pK values. Of course, treatment of microspeciation is not possible in this approach. Software in this group... 

More recently, software has been developed that predicts H, C, and N chemical shift values of proteins from either 3D stmcture files, for example, SHIFTS (6), SHIFTX (7), and SPARTA (8), or from the mere amino acid sequence using SHIFTY (9). First results have been reported on the de novo stmcture determination of proteins using fragment-based chemical shift predictions and molecular modeling (10, 11). 

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