The hydration of nucleic acid duplexes as assessed by a combination of volumetric and structural techniques

Using high precision densimetric and ultrasonic measurements, we have deter mined, at 25 degrees C, the apparent molar volumes phi V and the apparent m olar compressibilities phi K-S, of four nucleic acid duplexes-namely, the D NA duplex, poly(dIdC)poly(dIdC); the RNA duplex, poly(rA)poly(rU); and the Two DNA/RNA hybrid duplexes, poly(rA)poly(dT) and poly(dA)poly(rU). Using a vailable fiber diffraction data on these duplexes, we have calculated the m olecular volumes as well as the solvent-accessible surface areas of the con stituent charged, polar, and nonpolar atomic groups. We found that the hydr ation properties of these nucleic acid duplexes do not correlate with the e xtent and the chemical nature of the solvent-exposed surfaces, thereby sugg esting a more specific set of duplex-water interactions beyond general solv ation effects. A comparative analysis of our volumetric data on the four du plexes, in conjunction with available structural information, suggests the following features of duplex hydration. (a) The four duplexes exhibit diffe rent degrees of hydration, in the order poly(dIdC)poly(dldC) > poly(dGdC)po ly(dGdC) > poly(dAdT)poly(dAdT) approximate to poly(dA)poly(dT). (b) Repeti tive AT and TC sequences within a duplex are solvated beyond general effect s by a spine of hydration in the minor groove, with this sequence-specific water network involving about 8 additional water molecules from the second anti, perhaps, even the third hydration layers. (c) Repetitive GC and IC se quences,within a duplex are solvated beyond general effects by a "patch of hydration hydration" in the major groove, with this water network involving about 13 additional water molecules from the second and, perhaps, even the third hydration layers. (d) Random sequence, polymeric DNA duplexes, which statistically lack extended regions of repetitive AT, GC, or IC sequences, do not experience such specific enhancements of hydration. Consequently, c onsistent,vith our previous observations (T. V. Chalikian, A. P. Sarvazyan, G. E. Plum, and K. J. Breslauer, Biochemistry, 1994, Vol. 33, pp. 2394-240 1), duplexes with approximately 50% AT content exhibit the weakest hydratio n, while an increase or decrease from this AT content causes enhancement of hydration, either due to stronger hydration of the,major groove (an increa se in AT content) or due to stronger hydration of the major groove (an incr ease in GC content). (e) In dilute aqueous solutions, a B-DNA duplex is mor e hydrated than an A-DNA duplex, a volumetric-based conclusion that is in a greement with previous results obtained on crystals, fibers, and DNA soluti ons in organic solvent-water mixtures. (f) the A-like, RNA duplex poly(rA)p oly(rU) and the structurally similar A-like, hybrid duplex poly(rA)poly(dT) , exhibit similar hydration properties, while the structurally distinct A-l ike, hybrid duplex poly(rA)poly(dT) and non-A-like, hybrid duplex poly(dA)p oly(rU) exhibit differential hydration properties, consistent with structur al features dictating hydration characteristics. We discuss how volumetric characterizations, in conjunction with structural studies, can be used to d escribe, define, and resolve the general and sequence/conformation-specific hydration properties of nucleic acid duplexes, (C) 1999 John Wiley & Sons, Inc.