Side-chain theory

If we assume that those peculiarities of the toxin which cause their distribution are localized in a special group of the toxin molecules and the power of the organs and tissues to react with the toxin are localized in a special group of the protoplasm, we arrive at the basis of my side chain theory. The distributive groups of the toxin I call the haptophore group and the corresponding chemical organs of the protoplasm the receptor. . .. Toxic actions can only occur when receptors fitted to anchor the toxins are present. 

Figure 5.1 Comparison of receptor models beginning with (A) Ehrlich s first pictorial representation of his side-chain theory in 1898, (B) scheme of drug-receptor interaction in 1971, (C) acetylcholine ion-channel in 1982, and (D) G-protein-coupled receptor system in 1989.

From his pursuit of this goal was born the concept of selective toxicity, receptor theory, side chain theory, intrinsic activity, and affinity. Ehrlich was a prophet of almost biblical proportions, and much of what he predicted intuitively continues to be confirmed experimentally through... 

Bordet s Conception — Side Chain Theory of Rliriicli- —... 

Ehrlich was the first to explain the action of toxic substances and drugs. In what he called his side-chain theory, he explained that these substances affect only cells that have matching molecular fragments extending from their surfaces. Today we call these side chains receptors—the parts of cell surface molecules that extend outside the cell and interact with external messengers and drugs. They are still the object of intensive research. 

The term was coined by Paul Ehrlich at the end of the nineteenth century when he developed in his side-chain theory to explain the immune response. 

FIG. 6.1 Ehrlich s explanation of immunochemistry in his own symbols (from a letter to Carl Weigert, 1898, in which he gives the first pictorial representation of his side-chain theory). (Heymann, 1928.)... 

The separation of Hquid crystals as the concentration of ceUulose increases above a critical value (30%) is mosdy because of the higher combinatorial entropy of mixing of the conformationaHy extended ceUulosic chains in the ordered phase. The critical concentration depends on solvent and temperature, and has been estimated from the polymer chain conformation using lattice and virial theories of nematic ordering (102—107). The side-chain substituents govern solubiHty, and if sufficiently bulky and flexible can yield a thermotropic mesophase in an accessible temperature range. AcetoxypropylceUulose [96420-45-8], prepared by acetylating HPC, was the first reported thermotropic ceUulosic (108), and numerous other heavily substituted esters and ethers of hydroxyalkyl ceUuloses also form equUibrium chiral nematic phases, even at ambient temperatures. 

P Koehl, M Delarue. Application of a self-consistent mean field theory to predict protein side-chains conformation and estimate their conformational entropy. J Mol Biol 239 249-275, 1994. 

A common use of statistics in structural biology is as a tool for deriving predictive distributions of strucmral parameters based on sequence. The simplest of these are predictions of secondary structure and side-chain surface accessibility. Various algorithms that can learn from data and then make predictions have been used to predict secondary structure and surface accessibility, including ordinary statistics [79], infonnation theory [80], neural networks [81-86], and Bayesian methods [87-89]. A disadvantage of some neural network methods is that the parameters of the network sometimes have no physical meaning and are difficult to interpret. 

An a helix can in theory be either right-handed or left-handed depending on the screw direction of the chain. A left-handed a helix is not, however, allowed for L-amino acids due to the close approach of the side chains and the CO group. Thus the a helix that is observed in proteins is almost always right-handed. Short regions of left-handed a helices (3-5 residues) occur only occasionally. 

Peters, D., and J. Peters. 1982. Quantum Theory of the Structure and Bonding in Proteins Part 13. The p branched hydrocarbon side chains valine and isoleucine. J. Mol. Struct. (Theochem) 88,157-170. 

For the united atom models of realistic polymers the wall PRISM theory predicts interesting structure near the surface [95]. For example, the side chains are found preferentially in the immediate vicinity of the surface and shield the backbone from the surface. This behavior is expected from entropic considerations. Computer simulations of these systems would be of considerable interest. 

The non-collective motions include the rotational and translational self-diffusion of molecules as in normal liquids. Molecular reorientations under the influence of a potential of mean torque set up by the neighbours have been described by the small step rotational diffusion model.118 124 The roto-translational diffusion of molecules in uniaxial smectic phases has also been theoretically treated.125,126 This theory has only been tested by a spin relaxation study of a solute in a smectic phase.127 Translational self-diffusion (TD)29 is an intermolecular relaxation mechanism, and is important when proton is used to probe spin relaxation in LC. TD also enters indirectly in the treatment of spin relaxation by DF. Theories for TD in isotropic liquids and cubic solids128 130 have been extended to LC in the nematic (N),131 smectic A (SmA),132 and smectic B (SmB)133 phases. In addition to the overall motion of the molecule, internal bond rotations within the flexible chain(s) of a meso-genic molecule can also cause spin relaxation. The conformational transitions in the side chain are usually much faster than the rotational diffusive motion of the molecular core. 

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