Receptor conformational analysis

DM Mottola, S Laiter, VJ Watts, A Tropsha, SW Wyrick, DE Nichols, P Mailman. Conformational analysis of d dopamine receptor agonists Pharmacophore assessment and receptor mapping. J Med Chem 39 285-296, 1996. 

Paluchowska et al. (2002) reported the synthesis, pharmacological studies, and conformational analysis utilizing classical molecular modeling approaches of some arylpiperazine or 1,2,3,4-tetrahydroisoquinoline derivatives of the known and flexible 5-HT ia receptor ligands with different intrinsic activities at nanomolar levels [63]. The SAR is shown in Table 4. The synthetic steps involved for some of the compounds mentioned in Table 4 are shown in Scheme 2 [63]. 

In conclusion, the result of a conformational analysis is a structure which is in agreement with the experimental data. There may be other structures which also fulfill the experimental restraints and the bioachve conformahon may differ in distinct receptors [117]. Thus, the more data are acquired the higher is the probability that the structure is correct . 

Figure 2 Spatial overlap of low energy conformers of H-Hat-D-O rn-Aic-Glu-NH2 (heavy lines) with proposed models of the p-receptor-bound conformation (light lines) based on conformational analysis of H-Tyr-D-0 rn-Phe-As p-NH2 [24] (left panel) and H-Tyr-Pro-Phe(NMe)-D-Pro-NH2 (PL017) [29] (right panel). 

To study the presumed additional ligand-receptor interactions mentioned earlier in more detail, a conformational analysis was performed on a subset of compounds cho-... 

KARMA is an interactive computer assisted drug design tool that incorporates quantitative structure-activity relationships (QSAR), conformational analysis, and three-dimensional graphics. It represents a novel approach to receptor mapping analysis when the x-ray structure of the receptor site is not known, karma utilizes real time interactive three-dimensional color computer graphics combined with numerical computations and symbolic manipulation techniques from the field of artificial intelligence. 

Knowledge about drugs in general, for example, chemical structures and properties of known drugs, rules of conformational analysis and thermodynamics of receptor-ligand interactions. 

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