Water with biomolecules

Amadasi, A., Spyrakis, E., Cozzini, P., Abraham, D.)., Kellogg, G. E Mozzarelli, A. Mapping the energetics of water-protein and water-ligand interactions with the natural HINT force field predictive tools for characterizing the roles of water in biomolecules. J. Mol. Biol. 2006, 358, 289-309. 

Depicted in Fig. 2, microemulsion-based liquid liquid extraction (LLE) of biomolecules consists of the contacting of a biomolecule-containing aqueous solution with a surfactant-containing lipophilic phase. Upon contact, some of the water and biomolecules will transfer to the organic phase, depending on the phase equilibrium position, resulting in a biphasic Winsor II system (w/o-ME phase in equilibrium with an excess aqueous phase). Besides serving as a means to solubilize biomolecules in w/o-MEs, LLE has been frequently used to isolate and separate amino acids, peptides and proteins [4, and references therein]. In addition, LLE has recently been employed to isolate vitamins, antibiotics, and nucleotides [6,19,40,77-79]. Industrially relevant applications of LLE are listed in Table 2 [14,15,20,80-90]. 

Clementi, E., F. Cavallone, and R. Scordamaglia. 1977. Analytic Potentials from ab Initio Computations for the Interaction Between Biomolecules. 1. Water with Amino Acids. J. Am. Chem. Soc. 99, 5531-5545. 

Figure 9.60 Many different thiol-containing linkers can be used to prepare water-soluble QDs. The monothiol compounds suffer from the deficiency of being easily oxidized or displaced off the surface, thus creating holes for potential nonspecific binding. The dithiol linkers are superior in this regard, as they form highly stable dative bonds with the semiconductor metal surface that do not get displaced. The PEG-based linkers are especially effective at creating a biocompatible surface for conjugation with biomolecules.

This technique is widely used on water-soluble biomolecules—proteins, peptides, and carbohydrates in particular. The result is a spectrum whose major peaks consist of the molecular ion with a different number of charges attached. A molecular ion of, for example, about 10,000 Da with a charge (z) of 10 would behave in a mass spectrometer as though its mass were about 1000 daltons. Its mass, therefore, can be determined with a spectrometer of modest resolution—and cost. 

Electrospray ionization (ESI) was first employed more than 20 years ago, but it is fairly recently that it became a routine technique for the soft ionization of a wide range of polar analytes, including biomolecules. For this technique, the analyte is usually dissolved in a mixture of an organic solvent (most commonly acetonitrile or methanol) and water with a pH modifier [e.g. formic (methanoic) or acetic (ethanoic) acid for positive ion mode]. The presence of the pH modifier ensures that ionization takes place in the solution state. This is the only common case where ionization occurs before ion vaporization the exact mechanism of the vaporization (Figure 5.6) is still not clearly understood in ESI. 

A review of water in biology, including discussion of the physical structure of liquid water, its interaction with biomolecules, and the state of water in living cells. 

In blood plasma, the chloride ion concentration is sufficiently large (about 100 mAf) to prevent cis-Pt hydrolysis, and the neutral platinum species most likely crosses the cell membrane. Inside the cell the chloride ion concentration is much lower (about 4mM), which allows for hydrolysis (35, 37). Because water is a far better leaving group than chloride or hydroxide (38, 39), the aqua species are most likely the reactive form of cis-Pt in vivo. Thus hydrolysis is the rate-limiting step in the reaction of cis-Pt with biomolecules such as proteins, RNA, and DNA (40). 

One of the major objectives of the physical chemistry studies in water and biomolecules is to fully reproduce the experimentally observed folding/ unfolding behavior of a typical model protein in water by means of molecular simulation. However, the all-atom molecular dynamics (MD) simulation of the folding of a protein from the fully unfolded state to the native structure remains computationally intractable when the size of the target protein is larger than 100 residues and when simulation is carried out with explicit water molecules (i.e., when complete, contextualized simulation is attempted) [1-3]. 

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