Comparison of Mode Analyses at Different Resolutions Applied to Nucleic Acid Systems

¹ Univ. Wisc. Madison
² University of Wisconsin, Madison

^* To whom correspondence should be addressed. E-mail: cui{at}chem.wisc.edu.

Submitted on May 4, 2005
Revised on June 15, 2005
Accepted on 1 August 2005

	Abstract

More than two decades of different types of mode analyses has shown that these techniques can be useful in describing large-scale motions in protein systems. A number of mode analyses are available and include: Quasi-Harmonics, Classical Normal Mode, Block Normal Mode, and the Elastic Network Model. Each of these methods has been validated for protein systems and this variety allows researchers to choose the technique that gives the best compromise between computational cost and the level of detail in the calculation. These same techniques have not been systematically tested for nucleic acid systems, however. Given the differences in interactions and structural features between nucleic acid and protein systems, the validity of these techniques in the protein regime cannot be directly translated into validity in the nucleic acid realm. In this work we investigate the usefulness of the above mode analyses as applied to two RNA systems, the hammerhead ribozyme and a guaniner iboswitch. We show that Classical Normal Mode analysis can match the magnitude and direction of residue fluctuations from the more detailed, anharmonic technique, Quasi-Harmonic analysis of a Molecular Dynamics trajectory. The Block Normal Mode approximation is shown to hold in the nucleic acid systems studied. Only the mode analysis at the lowest level of detail, the Elastic Network Model, produced mixed results in our calculations. We present data that suggest that the Elastic Network Model, with the popular parameterization, is not best suited for systems that do not have a close packed structure; this observation also hints at why Elastic Network Model has been found to be valid for many globular protein systems. The different behaviors of Block Normal Mode analysis and the Elastic Network Model, which invoke similar degrees of coarse-graining to the dynamics but use different potentials, suggest the importance of applying a heterogeneous potential function in a robust analysis of the dynamics of biomolecules, especially those that are not closely packed. In addition to these comparisons, we briefly discuss insights into the conformational space available to the hammerhead ribozyme.

Key Words: Normal mode analysis, coarse-graining, elastic network, nucleic acid flexibility, quasi-harmonic analysis

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