Molecular modeling known receptors

The biological properties of dioxin include an ability to bind to a protein known as the AH (aromatic hydrocarbon) receptor Dioxin IS not a hydrocarbon but it shares a certain structural property with aromatic hydrocarbons Try constructing molecular models of dioxin and anthracene to see these similarities... 

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]. 

Objectives Optimize biological activity of drugs Find new active lead compounds Characteristics Response in isolated systems Effects are specific and well defined Specific mechanism of action Receptor is known in most cases Techniques Hansch Approach Multivariate Analysis Computerized molecular modeling Estimate rates of fate processes Analyze Processes Whole organism response Net effects (mortality growth, etc.) Specific nonspecific mechanisms Receptor unknown in most cases Hansch Approach Multivariate Analysis Molecular modeling not applied... 

The histamine H3 receptor has not been cloned yet and hence, virtually nothing is known about the receptor topography. However, ligand based molecular modelling studies have contributed to the understanding of the molecular features involved in ligand-receptor interaction. 

Although not very numerous, sweet macromolecules, both natural (Morris, 1976) and synthetic (Zaffaroni, 1975), are crucial for an understanding of the mechanism of the sweet receptor. The best known among proteins with a very strong sweet taste are brazzein (Ming and HeUekant, 1994), monellin, and thaumatin (Kurihara, 1992). Figure 5 shows molecular models of these three proteins. Other two known sweet proteins are mabinlin (Kurihara, 1992) and hen egg white (HEW) lysozyme (Maehashi and Udaka, 1998), whereas miraculin and curculin, which taste sweet when combined with sour substances, can be better described as taste-modifier proteins (Kurihara, 1992). 

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