Conformational modeling

Conformational analysis has been used to find and predict conformations which maximize antibiotic activity, using x-ray crystal stmctures coupled with nmr and cd spectra. An early approach utilized the Dale diamond lattice conformational model (480), which was extended to other diamond lattice models (472,481—483). Other studies have reHed on nmr data (225,484—491). However, extensive correlations between conformation and biological activity have not been successful (486,492). 

Figure 5 shows a conformational model of OMTS for discussion the solid state spectra. At the left a tilted crown type conformation is shown, where the carbons oc-... 

Fig. 5. Conformational model of octamethyltetrasiloxane left tilted crown conformation right untilted crown conformation. Big circles represent the Si-atoms. (Ref. 10))...

It is worth to note that the conformation model of Z-dol is speculated upon based on the observations of spreading, but detailed molecular arrangements are difficult to know owing to the limitation of instruments. Computer simulations such as the Monte Carlo (MC) and molecular dynamics (MD) were also performed in expecting to detect such infor-... 

At this point it is essential to compare the calculated structure with both the experimental data and the results of the rMD run (6). On the one hand, the interatomic distances of the final model must match the NMR restraints additionally, the fMD-averaged structure should correspond with the refined conformation obtained by the rMD. Only if the rMD and the fMD simulations result in the same conformational model and no experimental restraints are severely violated the calculated structure can be presented as a 3D image (7). 

In the case of being successful in calculating multiple conformations by using time- or ensemble-averaged MD restraints the solved molecular structures are presented as 3D models and can be deposited in an electronic structure database (17). Finally, it is recommended to provide an accurate explanation of the procedures used for the structure elucidation because the application of different methods (NMR, DG, MD, SA, Monte-Carlo calculations. X-ray crystallography) may result in varying conformational models which do not implicitly display the real state of a molecule. This aspect should be always kept in mind when dealing with structure determination methods. 

Acyclic Ketones. The stereochemistry of the reduction of acyclic aldehydes and ketones is a function of the substitution on the adjacent carbon atom and can be predicted on the basis of the Felkin conformational model of the TS,63 which is based on a combination of steric and stereoelectronic effects. 

In this model the function of RasGAP was to accelerate the isomerization step and to bring Ras into a conformation competent for GTP cleavage without further support of GAP residues. A different analysis of the macroscopic readout interpreted the small change in amplitude as the hydrolysis reaction or the release of inorganic phosphate, and rejected the model of a GAP-induced conformational change in Ras [171], but this was again disputed by supporters of the conformational model [172]. 

Recently, a similar simple conformational model was successfully used to assign the absolute configurations of acyclic and cyclic sul-finic esters (108). 

The Guy open conformation model docked structure was minimized in vacuo followed by a 1-ns molecular dynamics simulation of the complex embedded in a phosphatidylethanolamine (POPE) lipid bilayer. Adjustments were made to the model, and simulations were repeated so that very little movement occurred during the hnal iterations. Similar methods were used to dock the two domains in transitional and resting states. However, these results are more tenuous as little experimental data is available. In particular, the position of the S4-S5 linker and its role in opening and closing the pore are uncertain. The supplemental movie accompanying reference 36 illustrates the open-to-close-to-open cycle resulting from the simulations. 

BRANT AND CHRIST Realistk Conformational Modeling of Carbohydrates 45... 

---