How water provides the impetus for molecular recognition in aqueous solution

RU Lemieux - Accounts of chemical research, 1996 - ACS Publications
RU Lemieux
Accounts of chemical research, 1996ACS Publications
This Account deals with my current views on matters related to molecular recognition in
general and to carbohydrate recognition by proteins in particular. The urge to summarize my
thoughts on the subject arose because of important but not widely appreciated
developments, especially on the role of water, since the publication1 in 1990 of an
autobiography for the American Chemical Society. The book ends with a brief coda on the
importance of hydration to the stability of complexes and the postulation of perturbed layers …
This Account deals with my current views on matters related to molecular recognition in general and to carbohydrate recognition by proteins in particular. The urge to summarize my thoughts on the subject arose because of important but not widely appreciated developments, especially on the role of water, since the publication1 in 1990 of an autobiography for the American Chemical Society. The book ends with a brief coda on the importance of hydration to the stability of complexes and the postulation of perturbed layers of water2 over what we later termed polyamphiphilic surfaces. 3
The popular notion that the dominating factor was the intermolecular attraction between the complementary surfaces did not seem plausible in view of the large excess of water. Hydrophobic effects exercised in the presence of complementarity seemed to offer the best answersbut how? At the beginning, an attempt was made to force interpretations of our experimental findings in terms of the natural entropy-driven tendency of nonpolar molecules to leave water. However, the enigma existed that associations of oligosaccharides with lectins that had been examined were enthalpic4 and, moreover, involved a decrease, rather than an increase, in entropy. Why? In fact, but unbeknown to me, the notion of perturbed water at molecular surfaces was incubating in the minds of biophysicists. This can be appreciated from the review in 1989 of the fluctuation theory of hydration forces by Kornyshev and Leikin5 and the appearance in 1993 of the paper entitled “Measured Change in Protein Solvation with Substrate Binding and Turnover” by Rand and co-workers. 6 Quite evidently, the subject was in need of precise structural information, at the atomic level, about the interacting surfaces.
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