Unusual properties of aqueous solutions of l-proline: A molecular dynamics study

Abstract

Aqueous solutions of the bioprotectant proline are simulated for solute molar fractions ranging from 2.0 · 10 À3 to 2.3 · 10 À1. Statistical analyses show that proline affects the water structure more strongly than glycine betaine and trimethylamine-N-oxide, two of the most effective bioprotectants widely diffuse in nature, and as strongly as tert-butyl alcohol, a protein denaturant which at high concentration self-aggregates. No evidence is found, however, that proline self-aggregates as it has been previously suggested to explain experimental findings on concentrated proline solutions. Nevertheless, the behavior of the diffusion coefficients of proline and water vs. solute concentration qualitatively agrees with such results.

Structure and Hydration of l-Proline in Aqueous Solutions

“…This flattening is most likely due to an insufficient number of water molecules being present in these solutions to form a second coordination shell. The absence of perturbation to the bulk water network in solutions also occurs with other large solute molecules at relatively high concentrations in aqueous solution such as tertbutyl alcohol, 37 which is a protein denaturing agent, 9 and the neurotransmitter acetylcholine. 22 Interestingly, this phenomenon was not observed in similar studies of glutamic acid where the addition of glutamate to solution resulted in a marked disruption to the bulk water structure even at concentrations lower than those measured here (1:28).…”

“…This view is also supported by a recent molecular dynamics study on proline in water that also finds no self-aggregation between proline molecules. 9 In its role as an osmoprotectant, it appears that proline is excluded from interacting with the protein itself 45 but rather acts as a "chaperone" to prevent denaturation and refolding of the protein in question. 8 From the results presented here, it appears that while proline has a somewhat weak interaction with other proline molecules in solution it has a fairly strong interaction with the surrounding water environment without significantly perturbing the bulk water structure.…”

Compounds of Amino Acids and Neutral Salts

“…This may be due to the fact that proline has a very high solubility in water as well as the fact that proline increases the solubility of other compounds (Schobert and Tschesche 1978;Civera et al 2005; and references therein). Nevertheless, the number of crystals in Table 4.6 alone is deceptive insofar as among these salts, there are several groups of isotypic series of rare earth element (plus yttrium) salts, which of course do not represent unique structure types.…”

Evidence for cooperative Na+ and Cl− binding by strongly hydrated l-proline

“…This is in line with previous investigations. 15,17,59 On the other hand, the PDFs g N1Ow (r), g O1Ow (r) and g O2Ow (r) (see Fig. 1 for atom labeling) of water around the hydrophilic sites of Pro exhibit well-defined maxima at r E 0.3 nm indicative of pronounced hydration ( Fig.…”

“…6,7,[15][16][17][18][19][20][21][22][23][24][25] Moreover, the available quantitative information is scattered considerably. For instance, hydration numbers range from 20, obtained in a MD simulation, 15 to 11-12 from statistical mechanics 23 to 8-9, obtained with neutron diffraction. 17 Although the importance of hydrogen bonding is well documented, information on the number and strength of the formed ProÁ Á ÁH 2 O H-bonds is contradictory.…”