Mimicking

Figure A3,12.2(a) illnstrates the lifetime distribution of RRKM theory and shows random transitions among all states at some energy high enongh for eventual reaction (toward the right). In reality, transitions between quantum states (though coupled) are not equally probable some are more likely than others. Therefore, transitions between states mnst be snfficiently rapid and disorderly for the RRKM assumption to be mimicked, as qualitatively depicted in figure A3.12.2(b). The situation depicted in these figures, where a microcanonical ensemble exists at t = 0 and rapid IVR maintains its existence during the decomposition, is called intrinsic RRKM behaviour [9].

By using an effective, distance-dependent dielectric constant, the ability of bulk water to reduce electrostatic interactions can be mimicked without the presence of explicit solvent molecules. One disadvantage of aU vacuum simulations, corrected for shielding effects or not, is the fact that they cannot account for the ability of water molecules to form hydrogen bonds with charged and polar surface residues of a protein. As a result, adjacent polar side chains interact with each other and not with the solvent, thus introducing additional errors. 

Several methods are being studied to enhance the stabiUty of peptide mimics and improve their stereochemical similarity to the endogenous peptides. For example, the tetrapeptide Cys—Val—Phe—Met, a potent inhibitor of Ras famesyltransferase, is proposed to exist in a turned conformation, which mimics the endogenous peptide during enzyme binding. This conformation is successhiUy mimicked by 3-amino-l-carboxymethyl-5-phenyl-benzodiazepin-2-onederivatives (198) (142). 

Elucidation of the stmctural requirements for dmg interaction at the recognition site is by the study of stmcture—activity relationships (SAR), in which, according to a specific biologic response, the effects of systematic molecular modification of a parent dmg stmcture are determined. Such studies have permitted the classification of discrete classes of pharmacological receptors. For example, the neurotransmitter acetylcholine acts at both peripheral and central receptors which are of at least three distinct types. The effects of acetylcholine are mimicked in smooth and cardiac muscles and secretory... 

A common strategy for treating chronic opiate addiction iavolves the substitution of methadone which can either be provided as maintenance therapy or tapered until abstinence is achieved. Naltrexone and buprenorphine [52485-79-7] have also been used ia this manner. The a2 adrenergic agonist clonidine [4205-90-7] provides some rehef from the symptoms of opiate withdrawal, probably the result of its mimicking the inhibitory effect of opiates on the activity of locus coerukus neurons. 

Finally, the activated 3-aminopyridazine AT-oxide (381), mimicking 6-aminouracil, cyclizes with /3-ketoesters to give the pyrido[2,3-c]pyridazin-7-one AC-oxide (382). A reduced fused... 

SENSORS BASED ON FREE-STANDING MOLECULARLY IMPRINTED POLYMER MEMBRANES. COMPUTATIONAL MODELLING OF SYNTHETIC MIMICKS OF BIORECEPTORS... 

The mechanism by which TBT causes these effects has been extensively stiidied. The androgenic effects of TBT appear to be caused by interference with steroid biosynthesis rather than by mimicking the action of testosterone at the androgen receptor. Exposure of female molluscs to TBT leads to an elevation in testosterone in the haemolymph. " Much of the experimental evidence... 

The elegant genetic studies by the group of Charles Yanofsky at Stanford University, conducted before the crystal structure was known, confirm this mechanism. The side chain of Ala 77, which is in the loop region of the helix-turn-helix motif, faces the cavity where tryptophan binds. When this side chain is replaced by the bulkier side chain of Val, the mutant repressor does not require tryptophan to be able to bind specifically to the operator DNA. The presence of a bulkier valine side chain at position 77 maintains the heads in an active conformation even in the absence of bound tryptophan. The crystal structure of this mutant repressor, in the absence of tryptophan, is basically the same as that of the wild-type repressor with tryptophan. This is an excellent example of how ligand-induced conformational changes can be mimicked by amino acid substitutions in the protein. 

Toxic reactions occur by several mechanisms activation of metabolism, production of reactive intermediates and subsequent reactions with cell macromolecules, changing receptor responses, or through abnormal defence reactions. Several compounds cause toxicity by mimicking the organism s own hormones or neurotransmitters, or activating the body s endogenous receptors in some non-physiological way. ... 

J. G. Gay, B. J. Berne. Modification of the overlap potential to mimick a linear site-site potential. J Chem Phys 74 3316-3319, 1981. 

Adsorption of hard sphere fluid mixtures in disordered hard sphere matrices has not been studied profoundly and the accuracy of the ROZ-type theory in the description of the structure and thermodynamics of simple mixtures is difficult to discuss. Adsorption of mixtures consisting of argon with ethane and methane in a matrix mimicking silica xerogel has been simulated by Kaminsky and Monson [42,43] in the framework of the Lennard-Jones model. A comparison with experimentally measured properties has also been performed. However, we are not aware of similar studies for simpler hard sphere mixtures, but the work from our laboratory has focused on a two-dimensional partly quenched model of hard discs [44]. That makes it impossible to judge the accuracy of theoretical approaches even for simple binary mixtures in disordered microporous media. 

We introduce, for the sake of convenience, species indices 5 and c for the components of the fluid mixture mimicking solvent species and colloids, and species index m for the matrix component. The matrix and both fluid species are at densities p cr, Pccl, and p cr, respectively. The diameter of matrix and fluid species is denoted by cr, cr, and cr, respectively. We choose the diameter of solvent particles as a length unit, = 1. The diameter of matrix species is chosen similar to a simplified model of silica xerogel [39], cr = 7.055. On the other hand, as in previous theoretical works on bulk colloidal dispersions, see e.g.. Ref. 48 and references therein, we choose the diameter of large fluid particles mimicking colloids, cr = 5. As usual for these dispersions, the concentration of large particles, c, must be taken much smaller than that of the solvent. For all the cases in question we assume = 1.25 x 10 . The model for interparticle interactions is... 

Our main focus in this chapter has been on the applications of the replica Ornstein-Zernike equations designed by Given and Stell [17-19] for quenched-annealed systems. This theory has been shown to yield interesting results for adsorption of a hard sphere fluid mimicking colloidal suspension, for a system of multiple permeable membranes and for a hard sphere fluid in a matrix of chain molecules. Much room remains to explore even simple quenched-annealed models either in the framework of theoretical approaches or by computer simulation. 

In Section 20.2, equations for tlie reliability of series and parallel systems are established. Various reliability relations are developed in Section 20.3. Sections 20.4 and 20.5 introduce several probability distribution models lliat are extensively used in reliability calculations in hazard and risk analysis. Section 20.6 deals witli tlie Monte Carlo teclinique of mimicking observations on a random variable. Sections 20.7 and 20.8 are devoted to fault tree and event tree analyses, respectively. 

Monte Carlo simulation, a procedure for mimicking observations on a random variable, pennits verification of results tliat ordinarily would require difficult inatliematical calculations or extensive experimentation. 

Agonist. A compound that elicits a biologic response by mimicking an endogenous substance. 

Model calculations have indicated that/3-poly(L-ma-late) displays a certain degree of isosterism with the pho-sphodeoxyribose backbone of DNA (and probably with the backbone of RNA) regarding the distance between the negative charges [22]. It is, therefore, possible that /3-poly(L-malate) mimicks DNA in many of its activities. 

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