GRID conformational flexibility

Only a few attempts to quantify this concept can be found in the literature. Molecular dynamics and - grid-based QSAR techniques have been developed more recently to account for conformational flexibility in compounds [Clark et al., 1992 Clark et al, 1993 Hahn, 1997]. 

Wasserman and Hodge (290) used molecular dynamics to dock thermolysin inhibitors to an approximate model of the enzyme, with flexibility in the active site (3 8 of 314 residues) and ligand and with the rest of the enzyme represented by a grid approximation. A solvation model was used to compensate for desolvation in complex formation. To get 22 of 25 runs to orient the hydroxamate function correctly, the hydroxamate oxygens of the starting conformation were initialized within 4 A of the zinc. If they were allowed to vary to 8 A, then only 3 of 24 runs placed the ligand correctly. Obviously, there is a serious sampling problem. 

While collapsed films of this polymer can be lifted off the surface on electron microscope grids, viewed under the light microscope they are seen to break under the action of surface forces within a few minutes. Electron diffraction observations are evidently not feasible, but good polarized IR spectra are obtainable (Figure 2). The parallel dichroism of the Amide A band (3300 cm ) and the Amide I band (1660 cm ), and the perpendicular dichroism of the Amide II band (1555 cm ) is strong evidence that the collapsed monolayer is in the a-helical conformation with the molecules aligned on the water surface more or less parallel to the barrier. There is not sufficient dichroism in the bands associated with the n-decyl side chain for it to be orientated predominantly either parallel or perpendicular to the backbone. Since the side chains are very flexible it is probable that during collapse of the monolayer the side chains fold to form a more compact non-dichroic structure. 

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