Geometric fitting

In the next step, the suggested models are translated into 3D space by subsequently combining the templates. Again, each model is assessed and ranked according to various structural criteria, such as the geometric fit of the 3D templates and non-bonding interactions (steric clashes). If none of the solu-... 

Figure 8.1. Lock and key model (a) geometrical fit, (b) complementary pattern of functional groups, (c) site preference due to the solvent effect. The ligand L may better fit site A, but it binds preferentially to site B due to the solvent effect...

Katchalski-Katzrr E (1992) Molecular smface recognition determination of geometric fit between proteins and their ligands by correlation techniques. Proc Natl Acad Sci 89 2195-2199... 

Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A. A., Aflalo, C., and Vakser, I. A. (1992). Molecular surface recognition Determination of geometric fit between proteins and their ligands by correlation techniques. Proc. Natl. Acad. Sci. USA 89, 2195-2199. 

A database of molecules is analyzed for fit with the receptor or binding pocket and optimized for maximization of steric interactions. During this procedure, the geometric fit of the target structure is optimized concurrently. 

For a linear model, the estimated activity y, (in log units) of a molecule (open circle on the graph) is a function of its geometric fit on the pharmacophore x, y, = a x, + b. The n observed activities (y, gray circles) are compared with the predictions y, with the three following sums ... 

Two hypotheses have been proposed (Eisenman, 1962 Mullins, 1975) to account for the high Na+/K+ selectivity in Na+ dependent transport systems. Mullins emphasizes a geometrical fit of the cation. Eisenman emphasizes the electrical field strength of the putative binding sites. Many of the predictions made by Eisenman have been borne out experimentally in the ion-coupled systems and are complemented by the construction of ion-specific glass electrodes (Eisenman, 1962). 

The need to improve geometric fit and avoid steric clashes. 

Natl. Acad. Sci. U.S.A., 89,2195 (1992). Molecular Surface Recognition Determination of Geometric Fit Between Proteins and Their Ligands by Correlation Techniques. 

The selection of additives can be guided by molecular visualizations of the crystal structure based on geometric fits ° or binding energy calculations. ... 

The most important property of cyclodextrins is their great ability to form stereoselective inclusion complexes with a variety of compounds. The inclusion complex is formed when the guest molecule, or at least its part, enters the cavity of cyclodextrin-host and covalent bondings are not formed. The main factors responsible for the stability of such a complex are the geometrical fitting of the guest molecule to the cyclodextrin cavity, the polarity of the guest, the temperature and the solvent. 

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