Protein time-dependence

Rate effects may not be chemical kinetic ones. Benson and co-worker [84], in a study of the rate of adsorption of water on lyophilized proteins, comment that the empirical rates of adsorption were very markedly complicated by the fact that the samples were appreciably heated by the heat evolved on adsorption. In fact, it appeared that the actual adsorption rates were very fast and that the time dependence of the adsorbate pressure above the adsorbent was simply due to the time variation of the temperature of the sample as it cooled after the initial heating when adsorbate was first introduced. 

Screening of compound libraries with medium throughput is only possible if the spectra can be recorded in a short period of time, and if one measurement gives simultaneously a number of answers. In practice, several ligands are usually measured in one protein sample, depending on the problem [5]. Mostly 10-20 ligands are combined to multiplexes, which need to be deconvoluted if a positive answer, as shown in Fig. 1 is obtained. The hits obtained maybe analyzed automatically or by hand through manual inspection of the spectra. 

Rothe, GM, Determination of Molecular Mass, Stoke radius. Frictional Coefficient and Isomer-Type of Non-denatured Proteins by Time-Dependent Pore Gradient Gel Electrophoresis, Electrophoresis 9, 307, 1988. 

Clore, G. M., Gronenbom, A. M. Theory of the time dependent transferred nuclear Overhauser effect applications to stmctural analysis of ligand-protein complexes in solution. J. Magn. Reson. 1983, 53, 423 2. 

Harper JD, Lansbury PT Jr. Models of amyloid seeding in Alzheimer s disease and scrapie mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu Rev Biochem 1997 66 385-407. 

Our method has evolved during many studies over the last two decades. These include studies on the effect of strong internal electric fields in crystals on optical transition dipole directions of nucleic acid bases [2, 3], QM-MM predictions of time-dependent solvatochromism on 3-methylindole (3MI) in water [4], and on tryptophan in several proteins [5-8]. More recently, the same techniques have been... 

Toptygin D, Gronenbom AM, Brand L (2006) Nanosecond relaxation dynamics of protein GB1 identified by the time-dependent red shift in the fluorescence of tryptophan and 5-fluorotryptophan. J Phys Chem B 110(51) 26292-26302... 

To work out the time-dependence requires a specific model for the movement of the paramagnet, for example, Brownian motion, or lateral diffusion in a membrane, or axial rotation on a protein, or jumping between two conformers, etc. That theory is beyond the scope of this book the math can become quite hairy and can easily fill another book or two. We limit the treatment here to a few simple approximations that are frequently used in practice. 

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