Computer graphics study

When we have access to an interesting protein structure and we would like to engineer the molecule, it is not enough to limit one s preparations to a computer graphics study of the local 3-D environment around the residue(s) in question. It... 

Figure 4.25 Circle packing, (left) In two dimensions, no more than four circles can be placed so that each circle touches all the others, with every pair touching at a different point. What happens in higher dimensions (right) An attractive computer-graphic study of circle packing.

In the computer graphic study, the fit of flutriafol does not correspond to 24-methylene-24,25-dihydrolanosterol, in the extended conformation, but with the side chain of the sterol... 

The reactivity of conjugated double bonds is well known [126] and we were able to perform Michael-type additions on the double bond of the dehydroproline residue. Computer graphics studies of pristinamycin 11 confirmed the accessibility of this functionality (see Sect. 5.1.4). 

Thermodynamic properties such as heats of reaction and heats of formation can be computed mote rehably by ab initio theory than by semiempirical MO methods (55). However, the Hterature of the method appropriate to the study should be carefully checked before a technique is selected. Finally, the role of computer graphics in evaluating quantum mechanical properties should not be overlooked. As seen in Figures 2—6, significant information can be conveyed with stick models or various surfaces with charge properties mapped onto them. Additionally, information about orbitals, such as the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), which ate important sites of reactivity in electrophilic and nucleophilic reactions, can be plotted readily. Figure 7 shows representations of the HOMO and LUMO, respectively, for the antiulcer dmg Zantac. 

SPACEEIL has been used to study polymer dynamics caused by Brownian motion (60). In another computer animation study, a modified ORTREPII program was used to model normal molecular vibrations (70). An energy optimization technique was coupled with graphic molecular representations to produce animations demonstrating the behavior of a system as it approaches configurational equiHbrium (71). In a similar animation study, the dynamic behavior of nonadiabatic transitions in the lithium—hydrogen system was modeled (72). 

It covers the principles of engineering drawings, computer graphics, descriptive geometry, and problem solving. The overall study of graphics involves the three basic aspects of terminology, skills, and theory. 

Langridge R. Computer graphics in studies of molecular interactions. Chem Industry (London) 1980 (12) 475-7. 

Figure 6. Conformation of cxjmpound 12, toxin C4, in the crystal lattice. Data from diffraction studies by S. D. Darling (13) computer graphics by T. Chambers.

Cluster analysis is far from an automatic technique each stage of the process requires many decisions and therefore close supervision by the analyst. It is imperative that the procedure be as interactive as possible. Therefore, for this study, a menu-driven interactive statistical package was written for PDP-11 and VAX (VMS and UNIX) series computers, which includes adequate computer graphics capabilities. The graphical output includes a variety of histograms and scatter plots based on the raw data or on the results of principal-components analysis or canonical-variates analysis (14). Hierarchical cluster trees are also available. All of the methods mentioned in this study were included as an integral part of the package. 

A computer graphics facility was then used with available crystal data, molecular orbital and molecular mechanics calculations/ infra-red and n.m.r. studies to construct a three dimensional model of the target enzyme active site (a cytochrome P-450) designed specifically to accommodate both the natural substrate (24 methylene 24 25 dihydrolanosterol) and these known antagonists in their minimum or low energy forms. 

Figure 3 Example of how computer graphics can simultaneously display six dimensions. The example comes from the study of the antibacterial activity of a set of related compounds. Each compound corresponds to one lollipop (a shape at the end of a vertical line. Six properties can be plotted for each compound. Three of the dimensions correspond to the axes (labeled Prop 1, Prop 2, and Prop 3). A fourth dimension is indicated by the kind of shape at the end of the vertical lines. The fifth dimension is indicated by the size of the shapes. A sixth dimension can be indicated by the color of the shapes.

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