Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Molecular Dynamics Simulations and Quantum Chemistry as Useful Complements to RNA Structural Bioinformatics

RNA molecules are characterized by astonishing variability of molecular interactions. RNA structural bioinformatics is a powerful tool to understand the connection between RNA sequences and their topologies and functions. However, the world of RNA molecules is so complex that the experimental techniques are not capable to provide all information needed for a full understanding of RNA molecules. Advance computational techniques such as explicit solvent molecular dynamics (MD) and quantum chemistry (QM) can fill some of the gaps in our knowledge (1-3). It is obvious that computational techniques have numerous major limitations and are notoriously prone to misuse (1). Nevertheless, when properly applied, computations can provide data that cannot be harvested by other techniques. For example, MD can classify intrinsic structural flexibilities of RNA building blocks which are strikingly variable and of functional importance (4,5). Thus simulations can complement the primarily static and averaged structural data. MD can be instrumental in studies of long-residency hydration that can be of structural, dynamical, or even catalytic relevance (4,6). Simulations can also map major binding sites of (monovalent) cations including those that are delocalized (fluctuating). MD is in addition efficient in testing effects of base substitutions and modifications, including variable protonation states. QM techniques are primarily designed to investigate the nature and magnitude of all kinds of molecular interactions in nucleic acids and provide link between the molecular structures and energies (2,3). Proper application of computational methods requires close cooperation with bioinformatics and experiment, and mutual understanding. I will briefly summarize advantages, limitations and areas of application of these methods, and illustrate their close relation with structural bioinformatics on several systems/problems: the dynamics of GTP-ase associated center RNA (5) and A-site finger of the large ribosomal subunit, nature of base stacking (one of the frequently misinterpreted interactions) (7) and classification of base?phosphate interactions. Molecular interactions in RNAs result in a complex jumble of competing forces and often a given interaction can play multiple roles in different contexts. Computations have a potential to give qualitative insights into the balance of forces in RNAs and complement experiments. While the biology of RNA is being rapidly discovered, the understanding of physics or physical chemistry of RNA is lagging behind, and in this area computations can help.

References and Footnotes
  1. S.E. McDowell, N. Spackova, J. Sponer, N.G. Walter: Molecular Dynamics Simulations of RNA: An In Silico Single Molecule Approach. Biopolymers 85, 169-184 (2007).
  2. J. Sponer, J. Leszczynski, P. Hobza: Electronic properties, hydrogen bonding, stacking and cation-binding of DNA and RNA bases. Biopolymers 61, 3-36 (2001).
  3. J. Sponer, F. Lankas, Eds., Computational studies of RNA and DNA. Dordrecht: Springer, 2006.
  4. F. Razga, J. Koca, J. Sponer, N.B. Leontin: Hinge-like motions in RNA kink-turns: the role of the second A-minor motif and nominally unpaired bases. Biophys J. 88, 3466-348 (2005).
  5. F. Razga, J. Koca, A. Mokdad, J. Sponer: Elastic properties of ribosomal RNA building blocks: molecular dynamics of the GTPase-associated center rRNA. Nucl. Acids Res. 35, 4007-4017 (2007).
  6. M.M Rhodes, K. Reblova, J. Sponer, N.G. Walter: Trapped water molecules are essential to structural dynamics and function of a ribozyme. Proc. Natl. Acad. Sci USA 103, 13380-13385 (2006).
  7. J. Sponer, P. Jurecka, I. Marchan, F. J. Luque, M. Orozco, P. Hobza: Nature of base stacking. Reference quantum chemical stacking energies in ten unique B-DNA base pair steps. Chem. Eur J. 12, 2854-2865 (2006).

Jiri Sponer

Institute of Biophysics
Acad. of Sciences
Kralovopolska 135
61265 Brno, Czech Republic

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phone: +420 541 517 333