Solvent accessibility studies

In the second part of the chapter, the application of MALDI mass spectrometry for probing noncovalent interactions will be discussed. While special precautions have to be taken to avoid dissociation of complexes during MALDI sample preparation and during the desorption/ionization step, there are some extremely useful features of MALDI that make it suitable for fast readout in solvent accessibility studies (via HDX) and even for the determination of noncovalent binding constants via the so-called SUPREX method. 

Breslow studied the dimerisation of cyclopentadiene and the reaction between substituted maleimides and 9-(hydroxymethyl)anthracene in alcohol-water mixtures. He successfully correlated the rate constant with the solubility of the starting materials for each Diels-Alder reaction. From these relations he estimated the change in solvent accessible surface between initial state and activated complex " . Again, Breslow completely neglects hydrogen bonding interactions, but since he only studied alcohol-water mixtures, the enforced hydrophobic interactions will dominate the behaviour. Recently, also Diels-Alder reactions in dilute salt solutions in aqueous ethanol have been studied and minor rate increases have been observed Lubineau has demonstrated that addition of sugars can induce an extra acceleration of the aqueous Diels-Alder reaction . Also the effect of surfactants on Diels-Alder reactions has been studied. This topic will be extensively reviewed in Chapter 4. 

The PSA represents a very useful property for predicting absorption. It is usually defined as those parts of the van der Waals or solvent-accessible surface of a molecule that are associated with hydrogen bond-accepting capability (e.g., N or O atoms) and hydrogen bond-donating capability (e.g., NH or OH groups). Three types of PSA have been used in studying absorption ... 

Fig. 4 Representative membrane-active peptides that have been studied by solid-state 19F-NMR. (a) The primary sequences show which positions were substituted (filled green boxes) or which ones could in principle be substituted (dotted green lines), (b) Characteristic conformations of the peptides in the membrane-bound state. The space-filling solvent-accessibility models emphasize the amphiphilicity by colouring hydrophobic residues in yellow and cationic side-chains in blue. (c) Observed structures and alignment states of the peptides as determined by 19F-NMR...

An alternative method to investigate DNA strand breakage by OH radicals considers the surface accessibility of hydrogen atoms of the DNA backbone [102]. The solvent accessibility is 80% for the sugar-phosphates and —20% for the bases. This method allows a more direct determination of reaction of OH radicals with the individual deoxyribose hydrogens [103,104]. Recent studies show trends in reactivity of OH radicals closely follow the accessibility of the solvent to various deoxyribose hydrogens [105,106]. 

Carrying out the same simulation that produces solvent-accessible surface displays, but locating the dots at the center of the probe molecule, produces the extended surface of the model. This display is useful for studying inter-molecular contacts. If the user brings two models together—one with extended surface displayed, the other as a simple stick model—the points of intermo-lecular contact are where the extended surface of one model touches the atom centers of the second model. 

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