Book of Abstracts: Albany 2003

category image Albany 2003
Conversation 13
Abstract Book
June 17-21 2003

Non-Watson-Crick Base Pairing and Hydration in RNA motifs: Molecular Dynamics of 5S rRNA Loop E.

Explicit solvent and counterion molecular dynamics simulations have been carried out for a total of >80 ns on the bacterial (Escherichia coli) and spinach chloroplast 5S rRNA Loop E motifs. The Loop E sequences form unique duplex architectures composed of seven consecutive non-Watson-Crick base pairs and characterized by a broad minimum of the electrostatic potential in the deep (major) groove. The bacterial loop E initial geometry was taken from the crystal structure (URL064). The starting structure of spinach chloroplast Loop E was modeled using isostericity principles and the simulations refined the geometries of the three non-Watson-Crick base pairs that differ from the consensus bacterial sequence. The deep groove of loop E motifs provides unique sites for cation binding. Binding of Mg2+ rigidifies Loop E and stabilizes its major groove at an intermediate width. Mg2+ cations observed by X-ray diffraction in the bacterial Loop E are stable in the simulations. They do not bind directly at the most negative sites, as these are buried too deeply inside the groove. The spinach chloroplast Loop E sequence tends to relocate the Mg2+ cations compared to the bacterial Loop E cation distribution. In the absence of Mg2+, the Loop E motifs show an unprecedented degree of inner-shell binding of monovalent cations and a wide range of deep groove widths, depending on the base sequence and the counterion distribution. The Na+ cations penetrate into the most negative regions inside the deep groove. The spinach chloroplast Loop E shows a marked tendency to compress its deep groove compared with that of Escherichia coli (which is almost identical to the bacterial consensus). Structures with very narrow deep groove essentially collapse around a string of Na+ cations with very long coordination times. The Loop E non-Watson-Crick base pairing is complemented by a number of highly specific hydration sites ranging from simple water bridges to complex hydration pockets involving up to five hydration centers hosting 2 to 3 long-residing water molecules. The ordered hydration is intimately connected with local conformational variations of the RNA molecule.

Kamila Réblová1
Nada Spacková2
Jaroslav Kocá1
Neocles B. Leontis3
Jiri Sponer2

1National Center for Biomolecular Research
Kotlarska 2
611 37 Brno, Czech Republic
2Institute of Biophysics
Academy of Sciences of the Czech Republic and National Center for Biomolecular Research
Kralovopolska 135
612 65, Brno, Czech Republic
3Chemistry Department and Center for Biomolecular Sciences
Bowling Green State University
Bowling Green, OH 43403

Kamila Reblova: kristina@physics.muni.cz
Nada Spackova: spackova@ibp.cz
Neocles B. Leontis: leontis@bgnet.bgsu.edu
Jiri Sponer: sponer@ibp.cz

References and Footnotes
  1. K. Reblova, N. Spackova, R. Stefl, K. Csaszar, J. Koca, N. B. Leontis, Jiri Sponer, Biophys. J. 2003, ?Non-Watson-Crick base pairing and hydration in RNA motifs: Molecular dynamics of 5S rRNA Loop E?, in press.