Published Test Cases

Many of the published papers in the field of de novo molecular design have had as their main focus the demonstration of the validity of their approaches with various test cases. A wide range of molecular targets has been 

The Pro-Phe amide linkage was used as a seed fragment for GROW, which was run in unrestricted mode (i.e., it was permitted to choose, at each position in the sequence, any one of the 20 naturally occurring amino acids). Of the sequences produced, that with the highest score was Ac-Pro-Trp-Trp-Phe-Arg-Arg-NH2 (the Ac-Pro fragment being retained from the inhibitor mentioned above). When synthesized and assayed, this compound was found to inhibit renin with a K-, of 30 xM. 

At the time the work was carried out, only one orientation of MVT-101 with the HIV-1 protease active site was known from crystallographic studies. It 

In another study reported by a group from Agouron Pharmaceuticals, the LUDI program was used to help design novel ligands for the protein FKBP-12, which plays an important role in signal transduction pathways.  

From the examples provided above, it is possible to highlight several points about the utility of current de novo design methodologies. First, it is clear that de novo design programs can be dl use in real-world drug design 

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Elamrani et al. 1996] Elamrani, S., Berry, M.B., Phillips Jr., G.N., McCammon, J.A. Study of Global Motions in Proteins by Weighted Masses Molecular Dynamics Adenylate Kinase as a Test Case. Proteins 25 (1996) 79-88 [Elcock et al. 1997] Elcock, A.H., Potter, M.J., McCammon, J.A. Application of Poisson-Boltzmann Solvation Forces to Macromolecular Simulations. In Computer Simulation of Biomoleeular Systems, Vol. 3, A.J. Wilkinson et al. eds., ESCOM Science Publishers B.V., Leiden... 

Download a copy of SCREEN (SCREEN can be downloaded from the publisher s site www.bh.com/companions/0750674997.) Try a few test cases (follow the examples in this chapter) to become familiar with the software. 

We start with examples of the sequential approach. With this approach, you begin with more routine experiments, ones that are reasonably likely to succeed (e.g., calibration or optimization procedures). The initial set of experiments can also serve as a test case and/or show that you can reproduce literature values. For example, Aga (P6) proposes first to explore conditions that will optimize immunoassay sensitivity, and Spain (P7) proposes to begin with a study of topography, using published methods and a self-assembled monolayer with a known structure. 

PM3(tm) is a version (1996, 1997) parameterized with d orbitals for geometries, but not for heats of formation, dipole moments, or ionization energies, for transition metals [77]. It was evaluated ca. 2000 by Bosque and Maseras [78], who also briefly mentioned 11 earlier (1996-1999) publications testing this method. The consensus seems to be that the method tends to be good for geometries but not for energies, and that its reliability has to be proved on a case by case basis [78]. There have since been many published tests of PM3(tm), a few of which are given in reference [79]. 

An important ENTAM activity is communicating test results. Test reports offer a summary of test results and the possibility to compare them for the best choice of machines. In Italy, in the case of an orchard sprayer, for example, ENAMA publishes test reports which include technical data (main and auxiliary tank, pump, filters, flow rate adjustment, fan, nozzles, anti-drip devices etc.), description of the machine, test results, comments on the performances, best conditions of use and, also, road regulations (they are different in each country) and safety check. 

This method was applied to the design of a tripeptoid library. Experimental work on that library had been described by Zuckermann et al. who had shown that a few members of the library had high affinities for a 1-adrenergic or p-opiate receptors. The results of that published work were used as a retrospective test case to evaluate the effectiveness of Focus-2D. 

The essentials of the SSEA for numerically compufed energy-normalized N-elecfron wavefunctions were published in 1994 by Mercouris ef al. [54], The firsf application was not only to the multiphoton ionization of H (whose specfrum is known exactly analytically), as a test case, but also to the multiphoton detachment of the four-electron Li negative ion, with two free channels, Li ls 2s S and ls 2p P°. Li (or Be) is the first system of fhe Periodic Table for which the proper description of the zero-order electronic structure requires a multiconfigurational Hartree-Fock (MCHF) description. In the context of the review of the SSEA, we also discuss briefly the formulation of the problem in terms of the full atom-EMF interaction,Vext(f), which is computationally convenient as well as necessary for certain problems involving, say, off-resonance coupling of Rydberg states, for which use of just the electric dipole term is inadequate [55-57]. 

Before we leave this subsection, we note that a few studies comparing various isomer generation techniques have been published in an attempt to provide both a validation of an algorithm against a test case and a comparison of a variety of methods for consistency and execution time. Such studies may also contain isomer generation lists of the type mentioned in the previous paragraphs. To the reader interested in these tests, we provide references. " ... 

The time evolution of some chosen quantities of the bubble is used as the benchmark quantities. These are the sphericity, bubble size, rising velocity, and the center of the bubble mass. In order to show the superior properties of our Level Set-based multiphase flow solver, we demonstrate here a mesh cmivergence study, which has unfortunately not been published so far by the original benchmark authors. To this end, the time evolution of the bubble shapes with respect to the given resolutions for the two test cases that are visible in Fig. 13.6 and the time evolution of the selected quantities as bubble sizes (in vertical and in the perpendicular symmetry directions) and sphericity is displayed in Fig. 13.7. As it may be seen from the mentioned graphical proofs a perfect convergence is achieved already on a relatively coarse resolution for test Case 1 and also in test Case 2 within the time period covering the initial 1.5 time units. Moreover, the mass loss in both cases... 

The national organizations are often relayed into each profession by a body created and financed by this profession and which undertakes all or part of the work in preparing the standards. In the petroleum industry, this role is carried out in France by the BNPet (Bureau de Normalisation du Petrole) and in Germany by the FAM (Fachausschuss Mineralol-und Brennstoffnormung), in the United Kingdom by the IP (Institute of Petroleum), and in the USA by the ASTM (American Society for Testing and Materials). In the first two cases, the standards are published only by the national organizations (AFNOR and DIN respectively), while the IP and the ASTM also publish their own documents, only some of which are adopted by the BSI and ANSI, respectively. 

Propeller size, pitch, and rotational speed may be selected by model tests, by experience with similar operations, or, in a few cases, by published correlations of performance data such as mixing time or heat transfer. The propeller diameter and motor power should be the minimum which meet process requirements. 

For a new process plant, calculations can be carried out using the heat release and plume flow rate equations outlined in Table 13.16 from a paper by Bender. For the theory to he valid, the hood must he more than two source diameters (or widths for line sources) above the source, and the temperature difference must be less than 110 °C. Experimental results have also been obtained for the case of hood plume eccentricity. These results account for cross drafts which occur within most industrial buildings. The physical and chemical characteristics of the fume and the fume loadings are obtained from published or available data of similar installations or established through laboratory or pilot-plant scale tests. - If exhaust volume requirements must he established accurately, small scale modeling can he used to augment and calibrate the analytical approach. 

The second case concerns the results, published by du Pont, of actual service life tests... 

As was the case with lanthanide crystal spectra (25), we found that a systematic analysis could be developed by examining differences, AP, between experimentally-established actinide parameter values and those computed using Hartree-Fock methods with the inclusion of relativistic corrections (24), as illustrated in Table IV for An3+. Crystal-field effects were approximated based on selected published results. By forming tabulations similar to Table IV for 2+, 4+, 5+ and 6+ spectra, to the extent that any experimental data were available to test the predictions, we found that the AP-values for Pu3+ provided a good starting point for approximating the structure of plutonium spectra in other valence states. However,... 

Similar conclusions concerning the effect of the anion and impurities in the ionic liquid on the cyclopropanation reaction have been drawn in a recently published study [47]. Ionic liquids with the formula [bmim][X], where X = OTf, NTf2, PFe, and BF4, were used. The catalyst used in this study was 6b-Cu(OTf). In all cases, good enantioselectivities (89-97% ee) were obtained and these are similar to those obtained in chloroform. The influence of the presence of halogen anions was tested by the addition of 5% [bmim] [Cl] or [bmim][Br] to [bmim][BF4]. In both cases, a catalytically inactive solution was obtained, showing the detrimental effect of these anions on the reaction. 

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