Macromolecular binding site

DREAM++ A set of programs (ORIENT++, REACT++ and SEARCH++) for docking computationally generated ligands into macromolecular binding sites University of California [31]... 

M] is the macromolecular binding sites concentration [T] is the template concentration... 

Receptors are macromolecular binding sites for low molecular weight molecules (ligands), such as hormones and neurotransmitters. As such they are crucial to the well-being of the body. Xenobiotic ligands bind with receptors and in doing so interrupt the normal functioning of the body. 

Gong K, Mailloux L, I ler/berg MC Salivary film expresses a complex, macromolecular binding site for Streptococcus sanguis. J Biol Chem 2000 275 8970-8974. 

Ca concentration is estimated to be 1.25 mM (total Ca + is 2.45 mM) with only minor variations. " We would thus expect that Ca ions in extracellular fluids play a very different role from that inside cells. To ensure Ca binding the macromolecular binding sites need have only a modest Ca affinity 10 to 10" M ), and since extracellular Ca does not seem to have a signaling function, the rates of Ca association or dissociation in proteinbinding sites need not be very high. 

Under conditions when (a) the time dependence of the electric field gradient causing the relaxation in the macromolecular binding site B can be described by a single correlation time b) the dif-... 

It should be noted that Eqs. (8.22) through (8.27L imply that the relaxation rates 1/T and 1/T2 of halide ions undergoing rapid exchange with macromolecular binding sites, may become unequal when they are characterized by large values of x. Non-equality of 1/T and I/T2 for halides have indeed been experimentally observed in a number of cases and used to calculate i (cf. discussion below). The quotient between 1/T and I/T2 determined at the same frequency, has proved to be of... 

Effects of Internal Motion at the Macromolecular Binding Site... 

One of the questions which first surfaces in a halide probe experiment is usually whether or not "fast exchange" conditions prevail. "Fast exchange" is here taken to imply that the rate of exchange of halide ions between a macromolecular binding site and the bulk exceeds the NMR relaxation rate in the binding site. If this is the case the Xg s may be neglected in Eqs. (8.33) and (8.36). 

Fig. 8.4 (A-N). The excess transverse relaxation rate, A(l/T2), of a halide nucleus in a hypothetical two-site system as a function of the total halide concentration [X ]. Site A represents "free halide ion in solution and site B represents a macromolecule binding site, [m] denotes the concentration of the macromolecule, Vq is the quadrupole coupling constant in the B-site, is the rotational correlation time characterizing the halide in the macromolecular binding site and Kb denotes the binding constant for halide ion to the B-site. The curves have been calculated using Eqs. (8.25) to (8.28) and Eq. (8.40). The results are shown for two different halide exchange mechanisms. Case I represents the "first order" mechanism of Eq. (8.31)...

Useful biological information can sometimes be obtained from studies of the competition between halide ions and other ions or small molecules for the same macromolecular binding sites. Formally, the halide NMR excess relaxation rate in a system of two classes of sites upon addition of a second ion or molecule Y competing for the X binding sites may be described by the equation ... 

As has already been mentioned earlier in this section the excess transverse and longitudinal relaxation rates may become unequal for halide ions undergoing rapid exchange with macromolecular binding sites characterized by large values of Tj. The quotient between the apparent T2 and T values is in reverse a convenient experimental parameter which may be employed for the determination of For the simple case of very rapid chemical exchange the following expression holds approximately for the ratio of the two excess relaxation rates in a two-site case ... 

Because these methods incorporate no knowledge of the struaure of the macromolecular binding site, any suggestions they make as to its nature are merely models that fit the structure-activity data. Because of the many assumptions involved in the alignment and choice of the bioactive conformation, as well as the necessarily limited information supplied by the structure—activity data, there is a high likelihood that the models will be incorrect in details. Proper use of the models is as hypotheses to guide further studies until more definitive information is available. In the discussion that follows, the methods are presented in the order of the date of their first use. 

It should be noted that chemical exchange of a quadrupolar nucleus to and from a macromolecular binding site also produces fluctuations in the electric field gradient sensed by the nucleus and thus provides a second mechanism for quadrupole relaxation. The effective correlation time will now be given by eq. 27... 

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