Methodological advances

The methodological advances just presented have brought the field of nucleic acid force field calculations to a point where results from the calculations can be used with reasonable confidence to aid in the interpretation of experimental data as well as to be used for scientific investigations that are not accessible to experiment. Accordingly, a number of studies based on MD simulations, as well as other methods, have been undertaken to study a wide array of biologically relevant events associated with DNA. A brief overview of some of these efforts follows. 

The on-line principle has also been extended into the field of detection (Fig. 8). Thus, it is now possible to record FTIR [27-31] and Raman spectra in situ [32, 33], and there have been considerable advances in the on-line coupling of thin-layer chromatography with mass spectrometry. Here it has been, above all, the research groups of Wilson [34-36] and Busch [37-40] that have made the necessary instrumental and methodological advances, so that TLC must no longer be viewed as merely a clean-up method. Rather it forms the essential central point for all these on-line coupling techniques. 

In addition to the methodological advances noted above, the Et3SiH variant was utilized in the total synthesis of three members of the allopumil-iotoxin family [ 15,16]. In one of the more complex examples, ynal substrate 1 was converted to product 2 in 93% isolated yield as a single diastereomer (Scheme 4). Simple removal of the protecting groups allowed completion of... 

This section describes the main methodological advances that will be used in subsequent selected applications, including (1) Development of fast semiempirical methods for multiscale quantum simulations, (2) Directions for development of next-generation QM/MM models, and (3) Linear-scaling electrostatic and generalized solvent boundary methods. 

In our opinion, investigations in the field of physiological and pathological peptiduria appear to have a very brilliant future. Further methodological advances, primarily in the development of uniform and standardized procedures making the results of different laboratories comparable, are, however, necessary before this trend of research gains an established position in clinical chemistry. 

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