Introduction

The discipline of chemometrics is now some 30 years old, the term being used for the first time in 1972 by Svante Wold. Although the number of pure chemometrics laboratories is quite small, the discipline is firmly established in the chemical community, with chemometrics papers appearing in a broad range of chemical journals. Moreover, two specialized chemometrics journals have been published for quite some time, and several textbooks have appeared 1-4 . A recent definition of the term...

Case Study 3 Fluticasone Propionate

As the final example, we consider the case of a steroid molecule, fluticasone propionate (FP C25H31F3O5S Fig. 12), which has pharmaceutical importance as a potent anti-inflammatory agent which suppresses inflammation of the bronchial passages in the lungs. FP has been found to exist in two different polymorphic forms. Form 1 can be obtained by crystallization from a variety of solvents (typically acetone), and the crystal structure of form 1 is known. In attempts to produce crystals of FP of...

Scoring Functions

The extent of interaction between two molecules is usually expressed quantitatively by an energy value, which is ultimately based on a model of the physical chemistry of atomic interactions. There is often a trade-off between the sophistication of a scoring function and its computational cost. Rapid screening methods use simple geometric or steric criteria to allow very large numbers of ligands to be docked to a given target. However, these often miss potentially important ligands or binding...

Indexing Powder Diffraction Data using GAs 941 Background

As discussed in section 9.2.1, the first stage of crystal structure determination from powder diffraction data involves determination of the unit cell by indexing the powder diffraction pattern. Clearly it is not possible to proceed with structure solution unless the correct unit cell has been found at this initial stage. In contrast to the recent advances in techniques for structure solution, there has been relatively little fundamental development of indexing methods since the pioneering work...

Applications of EAs to De Novo Design

The early 1990s saw intense research into the development of methods for the de novo design of novel compounds to bind to a receptor site of known structure. The many programs developed during this period are reviewed in 21-23 . The constraints on de novo design for this type of application have been described in the previous section. The representation of the constraints varies from one program to another, but all are based on the concept of localized interaction sites within a steric cavity....

Calculate weighted profile Rfactor Rwp for trial structure

And the experimental powder diffraction pattern (Fig. 2). The comparison between the experimental and calculated powder diffraction patterns is quantified using an appropriate R-factor. To date, almost all reported direct-space approaches have used the weighted profile R-factor Rwp, which is the R-factor normally used in Rietveld refinement 6 . The definition of RWD is where y (obs) is the intensity of the th data point in the experimental powder diffraction profile, _v (calc) is the intensity...

References

Kowalski, Chemometrics, John Wiley & Sons, New York, 1986. 2 R. G. Brereton, Chemometrics Application of Mathematics and Statistics to Laboratory Systems, Ellis Horwood, Chichester, UK, 1990. 3 D. L. Massart, B. G. M. Vandeginste, L. M. C. Buydens, S. de Jong, P. J. Lewi, J. Smeyers-Ver-beke (Eds.), Handbook of Chemometrics and Qualimetrics Part A, volume 20A of Data Handling in Science and Technology, Elsevier Science Publishers, Amsterdam, 1998. 4 B. G....

Diversity and Distance Calculation

The selection of diverse molecules or sublibraries out of a larger library is a combinatorial problem and thus, a computationally intensive task. Choosing n maximally diverse compounds out of a library of N compounds requires the evaluation of N subsets 14 . The diversity comparison of all molecules has a computational complexity of order 0(N2). Thus, in the case of large libraries, the full computational evaluation of all relationships becomes nonfeasible. The distance between two molecules in...

Conclusions

The previous sections have described the GAs that have been developed in our laboratory for a range of chemical structure handling applications other applications include the GOLD program mentioned previously 48 , the design of combinatorial libraries 49 and the analysis of protein 2-D NMR data 50 , inter alia. With the obvious exception of the initial, 2-D subgraph isomorphism application, we have found that GA-based ap proaches provide an effective way of handling the inherently combinatorial...

NMR Pulse Shapes

In analyzing complex spin systems by NMR, much effort has been devoted to solving the problem of exciting a spin system nonuniformly across a frequency band under investigation, for example, tailored excitation and solvent suppression sequences. The rationale for designing such sequences is usually based on the approximate Fourier transform relation between the time-domain pulse envelope and the frequency-domain excitation pattern. This fails, however, for pulses with large flip angles. In...