Known receptor sites

In actual practice, the exploration and the intensive studies related to the 3D structure of macromolecular targets may be regarded as the most vital and crucial requirement. The already mentioned two most prominent methods are  

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Shortly after discovering salvinorin A s effects, Siebert sent a sample to David Nichols who initiated a NovaScreenTM receptor site screening. The screening results were in contrast to those of all previously tested psychedelics. Salvinorin A did not affect any of the receptor sites tested, which included all of the likely known receptor sites for other psychedelics. 

In the past several decades there have been an astronomical growth towards the metieulous potential investigative researches earried out on 3D chemical databses to make a remarkable and noteworthy advancements in the prevailing proeess of designing drngs for both hypothetical as well as known receptor sites. 

Describe the following aspects with regard to the Known Receptor Sites with suitable expla-... 

Taste and smell, unlike sight and sound, are not induced by any known waves in the air, but are caused by the presence of certain specific, chemical compounds by interaction with certain receptor-sites. The power of reaction to chemical stimuli has evolved from the diffused, and confused, chemotactic sensitivity of the primitive protozoa through to man, where specialized organs have been developed. 

If opiates are such addictive and potentially lethal compounds, why does the body respond to them As with the cannabinoids (Chapter 7), it has been discovered that the body and brain possess numerous opiate-specific receptor sites. As many as nine receptor subtypes have been identified, with three of them being the most important p (mu), k (kappa) and 8 (delta). The finding that the distribution of opiate receptors did not parallel the distribution of any known neurotransmitter prompted the search for and identification of a number of endogenous compounds specific to these receptors. These enkephalins and endorphins are manufactured within the brain and other body systems (especially the gut and intestines) and form the body s natural response to pain. They appear to be produced in bulk chains of amino acids called polypeptides , with each active neurotransmitter being composed of around five amino acid molecules. These active neurotransmitters are subsequently cleaved from the larger polypeptides at times of demand for example, it has been demonstrated that the plasma levels of these active compounds rise during childbirth, traumatic incidents and vigorous physical exercise. 

Once the folded sequence is known, the biological and chemical properties of the protein can be predicted. In the development of drugs, for example, the intended target in the human body is a particular protein of known structure whose behavior can be altered (for the better) when a drug molecule binds to a receptor site on the target molecule. 

In a very broad overview of the structural categories one can state several statistical correlations with type of function. Hemes are almost always bound by helices, but never in parallel a//3 structures. Relatively complex enzymatic functions, especially those involving allosteric control, are occasionally antiparallel /3 but most often parallel a//3. Binding and receptor proteins are most often antiparallel /3, while the proteins that bind in those receptor sites (i.e., hormones, toxins, and enzyme inhibitors) are most apt to be small disulfide-rich structures. However, there are exceptions to all of the above generalizations (such as cytochrome cs as a nonhelical heme protein or citrate synthase as a helical enzyme), and when one focuses on the really significant level of detail within the active site then the correlation with overall tertiary structure disappears altogether. For almost all of the dozen identifiable groups of functionally similar proteins that are represented by at least two known protein structures, there are at least... 

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. 

Consider the two hypothetical situations illustrated in Figure 2. On the top is pictured a collection of individual fluorescent receptors, while on the bottom is pictured the same number of receptors, yet they are connected via a molecular wire conjugated polymer. In addition, suppose it is known that binding of the analyte paraquat (PQ) into a receptor causes a complete quenching ofits fluorescence. In the case of individual receptors, the binding of one analyte gives only a small diminution in the total intensity of emission observed. This is because each exciton is fixed on one molecule and cannot communicate with other receptor sites. 

The first step in that process occurs when a person is exposed to HIV (usually through sexual contact or transfer of blood from an infected to a healthy person). HIV travels through the bloodstream until it comes into contact with certain types of white blood cells that contain proteins known as CD4 (cluster designation 4) receptor sites on their surface. The virus then attaches itself to the CD4 receptor and injects a protein (called the p24 protein) into the host cell s interior. The p24 protein carries the genetic information that controls reproduction of HIV. 

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